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552 Cards in this Set
- Front
- Back
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what existed before the big bang
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energy
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what did we exist as originally
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only hydrogen and some helium
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6 elements essential for life
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sulfur, phosphorus, oxygen, nitrogen, carbon, hydrogen
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what created heavier elements necessary for life
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1 round of star formation and supernova explosions nuclear fusion
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what mustve happened before life formed
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meteorite bombardment
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is there a gap between when life could've existed and when it actually did
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yes
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what occurs at the center of the archaea bacteria and eukaryote circle
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core cell functionality is established
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what came to be before eukaryotes existed and after the oldest fossils, why
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photosynthetic bacteria, to oxygenate the environment
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what was developed in the early phase of the timeline
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protein motifs
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when does gene regulation begin
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eukaryotes to hominids
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origin of life
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"RNA world metabolism world and extraterrestrial source"
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explain RNA world as origin of life
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thought ribozymes were the 1st form of life but the problem is that its hard to make RNA
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explain metabolism world as the origin of life
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metabolism provided environment where precursors & RNA form. the problem is how could this system evolve
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protocells
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"first cells defines intracellular/extracellular space darwinian evolution"
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physical constraints on protocells
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Ca concentration
permeability of lipid bilayer |
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what kind of permeability did the first cell have
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it had a very leaky membrane
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what does more impermeable mean about the # of transporters
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more impermeable= more transporters
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how do u modify a solute so that it cant cross the membrane so easily
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add a hydrophilic group
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how was the Ca+2 concentration in the first cells
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low Ca+2 concentration
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what effect do calcium ions have
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"-cause aggregation of nucleic acids and proteins disrupt membrane structure"
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when were the cellular physiological properties established
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before the 1st common ancestor
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common thread among all cells
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high internal K+ ion concentration
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what percent of total body weight is water
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75%
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what percent of total number of molecules is water
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99%
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is pure water conductive
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NO
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characteristics of water molecule
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"polar molecule polar covalent bonds, electronegativity, dipole
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what causes surface tension
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strong interactions between water molecules
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what kind of bonding occurs between water molecules
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hydrogen bonding
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is water a good solvent? why or why not
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yes, its polar
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what is water a good solvent for
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acids, bases, salts
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what forms when NaCl+water
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solution of Na and Cl ions (hydration shell)
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what purpose does the cell membrane serve for charged molecules
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barrier to diffusion of charged molecules
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what makes up cell membrane
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"phospholipids lipid bilayer"
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parts of phospholipid
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"polar-hydrophilic-interacts with water
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amphipathic
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mixed chemical properties in the same molecules
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structure of lipid bilayer
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"-The hydrophobic tails point in towards the center of the bilayer
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describe hydrophobic core of the lipid bilayer
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thin layer of oil
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another name for cell membrane and why
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fluid mosaic model- integral membrane proteins 
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membrane thickness
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60A (6nm)= thin
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hydrophobic core thickness
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30A (3nm)= thin
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what is the membrane structural integrity determined by
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cytoskeleton
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what proteins are embedded in the cell membrane
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"-peripheral membrane proteins cytoskeletal glycoproteins"
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most common integral membrane proteins
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glycoproteins (sugar group on protein)
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protease
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enzyme that breaks down protein
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what kind of molecules diffuse through the lipid bilayer
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hydrophobic molecules
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examples of solute that can dissolve into lipid membrane
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oxygen, CO2, fatty acids, steroid hormones
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are pumps efficient
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NO
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how do polar and charged molecules cross the cell membrane
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membrane proteins
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pumps
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require energy in the form of ATP to move ions up concentration gradients
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ion channels
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facilitate diffusion of ions by creating pores in the cell membrane
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transporters
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don't directly require metabolic energy
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name membrane pumps
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"Na K-ATPase Ca-ATPase H-ATPase H K-ATPase"
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why do cells have high Na+ outside the cell
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cuz we all came from marine environment so extracellular fluid mimics that 
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Na K-ATPase
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pumps 3 Na+ out and 2 K+ in
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what occurs when ATPase phosphorylates proteins
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a conformational change which moves the binding site from inside to the outside
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another name for Na K-ATPase or Na K pump and why
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electrogenic pump cuz there's constant current flowing out of the cell
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intracellular and extracellular concentration of K+
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125 5
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intracellular and extracellular concentration of Na+
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12 120
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intracellular and extracellular concentration of Cl-
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5 125
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intracellular and extracellular concentration of Ca+2
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1E-4 2
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intracellular and extracellular concentration of A-
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108 0
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what is A-
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fixed anions sum of all the proteins amino acid inorganic ions nucleotides DNA RNA that are located inside the cell
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job of H-ATPase
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maintains intracellular pH (H+ ion concentration)
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job of H
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K-ATPase
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job of Ca-ATPase
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get Ca out of the cell
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what is the main way the cell stores energy
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ATP
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ion gradients as sources of cellular energy
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"-sources of chemical energy (secondary active transport) sources of electrical energy (membrane potential)"
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type of movement of transporters
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"-facilitated diffusion secondary active transport"
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direction of diffusion and facilitated diffusion
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high concentration to low concentration
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direction of active transport
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low concentration to high concentration
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what does passive glucose transporter
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do moves glucose from blood stream to cells
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can glucose just cross the membrane? why or why not
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NO because its polar
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Na-glucose symporter structure
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2 binding sites- 1 for Na and 1 for glucose and they both bind and cross the membrane. Net overall movement is Na & glucose into the cell
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what kind of transport is Na-glucose symporter
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secondary active transport
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cotransport
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both ions move in the same direction
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counter-transport
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ions move in opposite directions
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where can Ca ATPase pump Ca+2 into
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mitochondria ER cytoplasmic reticulum
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what can Ca+2 ions function as
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second messengers; they modulate the function of a large number of different proteins neurotransmitter release muscle contraction
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what makes Ca+2 a great second messenger
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a brief increase in Ca+2
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what does prolonged inc in Ca+2 concentration trigger
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cell death; blockade of blood flow
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what does decreases O2 lead to
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decreased ATP
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what is the primary determinant of changes in cell volume
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the flow of water into or out of the cell across the cell membrane
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aquaporins
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water channels
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osmolarity
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a measure of the concentration of osmotically active particles in a solution
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how is osmolarity expressed
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osmoles of solute per liter of solution
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what is the osmolarity for molecules such as glucose;sucrose; and urea
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1molar 1 osmole/liter solution
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what is the osmolarity of a 1M NaCl solution
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2 osmole/1 solution
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what is the osmolarity of extracellular solution kept in
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275-295 mosmole/l
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concentration of H2O molecules in pure water
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55.5M
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concentration of H2O molecules in a 1M glucose solution
|
54.5 M
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what do water molecules flow down their concentration gradient like
|
membrane permeable solutes
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is the cell sensitive to osmolarity
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YES
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what do aquaporin channels allow for
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water to flow down conc gradient
|
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what are electrochemical phenomenon
|
brain and muscle function
|
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voltages in cells are generally less than what
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100mV
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what range are currents in
|
nA (nanoamps)
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main mediator of small currents
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ion channels
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ion permeation
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how ions move through channels
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ion selectivity
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how we distinguish the different sorts of channels from eachother
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which has greater ion selectivity K or Na
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K;by 1:10
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K+ ion radius
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1.33 A
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Na+ ion radius
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.95A
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throughput
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how many ions flowing through every second
|
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throughput of K+
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10^8/second
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K channel structure
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2 membrane spanning domains (amino and carboxy terminal) and they assemble as a tetramer.
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is the K channel narrow or wide
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narrow
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selectivity filter
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string of amino acids in a straight line parallel to the pore
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2 components of space-filling model of K channel
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rigid pores and flexible sparse region (opens
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how do ions get across cell membranes
|
maintain inner hydration shell and can go 75% through water
|
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|
TVGYG
|
selectivity filter
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solid NaCl + water gives you what
|
solution of sodium and chloride ions (hydration shell)
|
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what's the molecular mimic of water
|
oxygen atoms
|
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what does a longer channel signify about the selectivity
|
longer channel=increased selectivity
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is the pore fixed
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YES
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what does increased energy barrier signify about ion flow
|
increased energy barrier= decreased flow of ions
|
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what direction is net flux always through
|
the channel
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how do K+ ions move in and out of the channel without encountering any large energy barriers
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cuz the 4-fold symmetry of the channel mimics the normal inner hydration shell of the ion
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how do ions move through the pore
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due to the constant flipping between 2 stable channel states
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why is it energetically less favorable for Na to come into the pore
|
Na can't pop along 4 side (to fit between O)
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what effect will a change in aa have
|
a change on pore function
|
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what is electrical flow produced by
|
movement of ions (diffusion)
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what are the primary electrical current carriers in the body
|
dissociated ions
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electrolytes
|
"cations-pos charge and anions-neg charge"
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direction of electrical current in aqueous solution
|
positive to negative
|
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anode
|
positive
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cathode
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negative
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what is a bulk solution with ions compared to
|
a resistor
|
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ohm's law
|
V=IR
|
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resting membrane potential
|
-60 to -90 mV
|
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what is the intracellular potential relative to extracellular
|
negative
|
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what provides a source of energy that can be converted to electrical potential energy
|
the non-equilibrium distribution of ions
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|
2 structural components that are necessary for the conversion to electrical potential energy
|
"1.ion-impermeant lipid bilayer which can produce a separation of charge
|
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what types of charges are highly reactive
|
unshielded charges
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cell membrane
|
thin nonconducting sheet separating 2 conducting surfaces (intracellular and extracellular)
|
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what makes a better capacitor
|
the thinner it is
|
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principle of electroneutrality
|
states that the sum of negative charges in solution must equal the sum of positive charges
|
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|
chemical potential difference
|
concentration gradient
|
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electrical potential difference
|
charged ion will be affected by electric field
|
|
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electrochemical equilibrium
|
combine electrical & chemical potential difference
|
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Nernst equation
|
Ei= 61.5/Z log ([C]o/[C]i) mV
|
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Ei
|
equilibrium potential for ion i
|
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Z
|
valence of the ion (+1 for Na & K
|
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[C]o
|
ion concentration outside the cell
|
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[C]i
|
ion concentration inside the cell
|
|
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what temperature does the nernst equation apply to
|
37 degrees
|
|
|
log (1/10)
|
-1
|
|
|
log (1)
|
0
|
|
|
log (10)
|
1
|
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log (100)
|
2
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equilibrium potential for K+ ions
|
-61.5 mV
|
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|
another name for nernst potential
|
equilibrium potential
|
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what is the equilibrium potential
|
electrical driving force=chemical driving force
|
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|
E_Cl
|
-86mV
|
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E_K
|
-86mV
|
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E_Na
|
61.5mV
|
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what is Vm (membrane potential) typically
|
-70mV
|
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what is used to maintain gradients
|
Na
|
|
|
what is the equilibrium potential drawn towards
|
Na potential
|
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|
what does the Goldman Equation tell us
|
the relationship between Vm
|
|
|
Goldman Equation
|
Vm=61.5 log([K+]o+b[Na+]o/[K+]i+b[Na+]i) mV
|
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|
what is b in the goldman equation
|
permeability of Na/K= .02
|
|
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2 factors that determine Vm membrane potential
|
"ion concentrations- determine the equilibrium potentials for each ion
|
|
|
what does depolarization do to the cell
|
makes it more positive
|
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what does hyperpolarization do to the cell
|
make it less positive
|
|
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when do u have zero net flux
|
when the membrane potential=equilibrium potential of the membrane
|
|
|
for a typical cell are most ions at equilibrium
|
NO
|
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|
what can ion flow across membranes be modeled as
|
an equivalent electrical circuit
|
|
|
what do ion channels function like
|
resistors
|
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|
membrane conductance
|
sum of all the ion channels in the membrane that are open at the time of the measurement
|
|
|
membrane capacitance
|
within a limited voltage range;the lipid bilayer functions like a pure capacitive element
|
|
|
membrane battery
|
the non-equilibrium ion distribution acts like a barrier providing electrical potential energy for the movement of ions (charge)
|
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what kind of force does the membrane batter produce
|
electromotive force
|
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|
what is membrane conductance due to
|
the presence of ion channel proteins
|
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|
do artificial lipid bilayers have high or low conductance
|
extremely low conductance
|
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what is the reciprocal of conductance
|
resistance
|
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what is the formula relating conductance and ohms
|
"Ohms=1/Siemmens
|
|
|
what is the formula relating I
|
g
|
|
|
driving force
|
the voltage that acts on an ion
|
|
|
driving force for K+ ions
|
"Vm-E_K membrane potential-equilibrium potential"
|
|
|
driving force for Na+ ions
|
Vm-E_Na
|
|
|
Ohm's Law including K+ driving force
|
I_K=g_k(Vm-E_K)
|
|
|
Ohm's law including Na+ driving force
|
I_Na=g_Na(Vm-E_Na)
|
|
|
what occurs when there's more open channels
|
more ions flow out of the cell and run down gradients
|
|
|
what is attached to S4
|
many positive residues
|
|
|
what responds to gradients
|
charges
|
|
|
S4
|
"voltage sensor- positively charged residues sense membrane potential
|
|
|
S4-S5 linker helix
|
connects the 2 domains
|
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|
what occurs when the membrane depolarizes
|
the channel opens
|
|
|
how many times did voltage sensitive channel evolve
|
just once
|
|
|
how many domains have the same evolutionary origin
|
4
|
|
|
what are kinetic states of voltage-gated channels dependant on
|
rate constants
|
|
|
what are the kinetic states of voltage gated channels
|
"1.closed- doesn't pass ions 2.open-passes ions 3.inactivated- doesn't pass ions"
|
|
|
what happens when u leave a channel open for a while
|
it becomes inactivated
|
|
|
is the recovery rate fast or slow
|
slow
|
|
|
what is slower activation rate or inactivation rate
|
inactivation rate
|
|
|
what allows the channel to be closed
|
a protein blocks the channel
|
|
|
what does the amino terminus correspond to
|
the protein that physically blocks the channel (responsible for inactivation)
|
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|
what is the inactivation particle
|
string of amino acids
|
|
|
action potential
|
transient voltage change produced by varying ion conductances
|
|
|
what is the AP produced by
|
K and Na channels
|
|
|
what does the nervous system do
|
rapidly transmits info. from one end of the animal to the other end.
|
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|
what does the AP allow for
|
for info. to quickly move from one end of the animal to the other end.
|
|
|
what does the cell function as
|
RC circuit
|
|
|
what functions as a capacitor in the cell
|
lipid bilayer
|
|
|
what functions as the resistor
|
ion channels
|
|
|
what are the 2 currents and order
|
current first flows to capacitor then resistor
|
|
|
what is the peak of the voltage determined by
|
ohm's law
|
|
|
why is there a lack of instant change in response to current
|
cuz current is flowing through the capacitor. only get instant change when current flows through resistor
|
|
|
what type of relationship exists between the stimulating current and response
|
proportional
|
|
|
what kind of relationship exists between the threshold stimulus and response
|
nonlinear- trigger an AP (large response)
|
|
|
characteristics of AP
|
"1.triggered by depolarization 2.threshold voltage level must be reached in order to trigger an AP 3.all-or-non events 4.membrane potential at peak of AP is positive (overshoot) 5.refractory period (where AP doesn't work well)"
|
|
|
another term for passive responses
|
sub-threshold responses
|
|
|
what kind of responses do sub-threshold currents produce
|
linear membrane responses
|
|
|
what kind of response do suprathreshold depolarizing current initiate
|
AP
|
|
|
what is the threshold potential typically
|
-50 to -40 mV
|
|
|
All or non phenomenon
|
doesnt matter how strong the stimulus is, once u trigger the threshold, u get an AP
|
|
|
relationship between height and duration of the AP and the nature of the stimulus
|
height and duration of AP are fixed & independent of the nature of the stimulus
|
|
|
relationship between amplitude and strength of supra-threshold stimulus
|
amplitude is independent of strength of supra-threshold stimulus
|
|
|
what does refractory period limit
|
how rapidly u can pump information
|
|
|
what do changes in relative permeabilities induce
|
action potential
|
|
|
what happens to conductance during AP
|
it increases
|
|
|
what kind of current do u get as Na channels open
|
more inward current
|
|
|
what turns on faster Na or K conductance
|
K conductance
|
|
|
which channel has faster kinetics K or Na
|
Na channel has faster kinetics
|
|
|
positive feedback relation
|
opening of voltage-gated Na+channels in membrane->incr. membrane Na+ permeability->inc. flow of Na+ into cell->increased membrane potential (depolarization)
|
|
|
why does the upstroke terminate
|
cuz channels inactivate and u have used up all the channels
|
|
|
what is the rapid termination of the AP due to
|
"-inactivation of the Na+ conductance, activation of K+ conductance"
|
|
|
what conductance is bigger K or Na
|
K conductance is bigger
|
|
|
what is the result of a larger K conductance
|
membrane potential becomes negative=hyperpolarization
|
|
|
what is hyperpolarization due to
|
the sustained increase in the K+ conductance following the action potential
|
|
|
absolute refractory period
|
inactivation of a majority of Na+ channels. doesn't matter how big a current, there'll be no AP
|
|
|
relative refractory period
|
increased K+ conductance and Na+ channel inactivation. stick a big enough of a current in, get AP
|
|
|
function of proteins in the cell membrane
|
to facilitate the movement of ions and polar molecules across the membrane.
|
|
|
where are peripheral membrane proteins located
|
on the inner surface of the cell membrane
|
|
|
what are transmembrane proteins and what are they typically known as
|
those that cross the cell membrane to the extracellular surface, typically known as glycoproteins
|
|
|
proteins that facilitate the movement of polar or charged molecules across the cell membrane
|
pumps, ion channels, transporters
|
|
|
how do membrane pumps function
|
"by translocating an ion binding
surface from inside the cell to outside the cell and then a modified surface from outside back to the inside of the cell." |
|
|
what is the movement of the ion binding surface provided by
|
by a conformational change in the shape of the protein
|
|
|
what is the conformational change in protein provided by
|
hydrolysis of ATP to ADP
|
|
|
what is the kinase function of the pump used for
|
to phosphorylate the pump protein, which then induces the first conformational change 
|
|
|
describe the flow of anions and cations
|
cations (+) move towards the cathode (-), anions (-) move towards the anode (+)
|
|
|
describe the hydration shell formed with Na and Cl ions
|
Na (+) interacts with O (-) and Cl (-) interacts with H (+)
|
|
|
describe ion selectivity
|
There are channels that only let K+ ions to pass and channels that only let Na+ ions to pass.
|
|
|
what ions is the cell membrane predominantly permeable to at rest
|
K+ ions
|
|
|
property of capacitance
|
the thin lipid bilayer has the ability to separate electric charges
|
|
|
what is a chemical potential difference due to
|
concentration gradient
|
|
|
what is an electrical potential difference due to
|
separation of charge
|
|
|
equilibrium potential
|
"the membrane potential at which the electrical and chemical potentials for a given ion are equal and opposite"
|
|
|
what does the Goldman equation provide
|
means to calculate the membrane potential when more than one ion is permeable.
|
|
|
example of facilitated diffusion
|
passive glucose transporter (moves glucose from blood stream into cells)
|
|
|
why are secondary active transporters called secondary
|
"because they use chemical energy stored in the form of an ion gradient rather than directly use ATP"
|
|
|
example of secondary active transport
|
Na+/glucose transporter
|
|
|
what is the Na+/glucose transporter used for
|
to actively transport glucose out of the intestines and into the blood stream and also out of the kidney tubules and back into the blood.
|
|
|
what does the LacY transporter do
|
"it mediates the coupled cotransport of lactose and protons (H+) down a proton gradient."
|
|
|
how are K channels assembled as
|
tetramers- they're assembled from 4 protein subunits
|
|
|
what are channels gated by
|
stimuli like changes in membrane voltage, changes in intracellular Ca2+ or H+ ion concentrations, binding of proteins known as G-proteins to the channel and covalent modification of the channel by phosphorylation.
|
|
|
sub-cellular compartments of a neuron
|
"-cell body (soma)
-dendrites (dendritic tree) initial segment (axon hillock) axon nerve terminal" |
|
|
what is the direction of flow of electrical info. through a neuron presynaptic
|
nerve terminal->dendrites/cell body of postsynaptic neuron->axon->nerve terminal->next neuron
|
|
|
where does the AP initiate, why?
|
initial segment, its a region of many Na+ channels
|
|
|
what are the passive electrical properties of axons known as
|
cable properties
|
|
|
what 2 directions can a current flow after being injected into the center of an axon
|
"1.flow axially along the interior of the axon
2.flow back to ground across the membrane" |
|
|
what does the relative amount of current that crosses the membrane versus the amount of current that flows axially dependent on
|
resistance of the membrane relative to the resistance of the axial current path
|
|
|
what happens to the current flowing down the nerve fiber and the amount of current crossing the membrane resistance with each increment in distance along the axon
|
they gradually decrement
|
|
|
what is the axon cable mathematically modeled as
|
a series of RC circuits connected together
|
|
|
what is the membrane resistance r_m
|
the resistance associated with each small segment of RC circuit
|
|
|
what is access resistance
|
resistance that links the segments of the RC circuit together
|
|
|
what is the equation for length constant (lambda)
|
sq. rt.(r_m/r_a)
|
|
|
what is the length constant
|
the distance over which the steady-state membrane potential drops to 37% of the original amplitude
|
|
|
when are the conduction properties of the cable best
|
when r_a is relatively small and r_m is relatively large (decreasing the axial resistance increases the length constant and increasing the membrane resistance, increasing the length constant)
|
|
|
what happens at the peak of the action potential
|
there's an inward flow of current carried by sodium ions
|
|
|
what happens after artificial injection of a current at one point in an axon, whats it called
|
currents flow for some distances from the point of current injection called local circuit currents
|
|
|
what is the distance over which local circuit current flow determined by
|
length constant
|
|
|
what does local circuit flow act for
|
to depolarize the cell membrane for some distance from the site of current injection
|
|
|
does the AP normally move in one direction? why or why not
|
yes, cuz the membrane region behind the AP wavefront is in the refractory period and unable to support a new AP
|
|
|
what direction does the axon conduct AP? whats it called
|
in either directions, its symmetric
|
|
|
what is the rate of current flow in a wire
|
speed of light
|
|
|
what is the rate of electrical conduction in an axon
|
varies over the range .1 to 100m/s
|
|
|
2 major factors that affect the rate of AP propogation
|
axial resistance and membrane resistance
|
|
|
what will result in more current flowing inside the axon
|
increasing membrane resistance of decreasing axial resistance
|
|
|
2 strategies to increase the speed of AP propagation
|
"1.decrease the resistance of the axial path down the inside of the axon by increasing the diameter of the axon
2. increase the resistance of the cell membrane with a specialized sheathing, myelin" |
|
|
more current flowing inside the axon allows for what
|
local circuit flow to spread over a greater length of the axon resulting in a greater spread of membrane voltage depolarization, which will initiate an AP further down the axon and speed up the rate of conduction
|
|
|
how do invertebrates increase speed of AP propagation
|
increase the diameter of the axon, which gives a greater cross-sectional area for current flow
|
|
|
what do vertebrates do to increase the speed of AP propagation
|
they produce a myelin sheath around the axon
|
|
|
what are myelin forming cells called
|
glial cells
|
|
|
what is myelin analogous to
|
plastic insulation wrapped around the copper wire of household electrical circuits
|
|
|
nodes of ranvier
|
periodic breaks in the myelin sheath
|
|
|
how does myelin alter current flow
|
by reducing the capacitance and resistance of internodal membrane, producing more efficient local circuit current flow
|
|
|
saltatory conduction
|
AP jumps from node to node
|
|
|
direction of integration
|
from the dendrites to the axon hilock
|
|
|
direction of self-propagating wave of depolarization
|
axon hillock to past the myelin sheath
|
|
|
invertebrate diameter
|
up to 1 mm
|
|
|
vertebrate diameter
|
1 to 20 micrometers
|
|
|
orthodromic action potentials
|
AP travels from the cell body down the axon towards the nerve terminal
|
|
|
antidromic action potential
|
action potential propagating from the nerve terminal to the cell body
|
|
|
2 broad classes of neurotransmitter receptors
|
"1.those that contain and integral ion channel thats gated by ligand binding
2.those that are G-protein linked" |
|
|
classic example of G protein linked receptor
|
adrenergic and muscarinic acetylcholine receptor
|
|
|
classic example of ligand gated ion channel
|
nicotinic acetylcholine receptor
|
|
|
most common neurotransmitters and what types of receptors they have
|
acetylcholine, GABA, glycine, and glutamate have both ligand gated ion channels and G protein linked receptors
|
|
|
what other neurotransmitters have both types of receptors
|
serotonin, histamine, and ATP 
|
|
|
characteristics of ligand-gated ion channels
|
"-integral ion channel, gated by ligand binding
-multiple subunits (3,4,or 5) -more than 100 genes in genome encode ligand-gated ion channel subunits -underlie fast synaptic transmission" |
|
|
examples of ligand gated ion channel neurotransmitters
|
"acetylcholine
GABA Glycine glutamate" |
|
|
acetylcholine receptor for ligand gated ion channel
|
nicotinic acetylcholine receptor
|
|
|
GABA receptor for ligand gated ion channel
|
GABA_A receptor
|
|
|
glycine receptor for ligand gated ion channel
|
glycine receptor
|
|
|
glutamate receptor for ligand gated ion channel
|
"3 main kinds:
AMPA receptor Kainante receptor NMDA receptor" |
|
|
characteristics of G-protein linked receptors
|
"-ligand binding activates G-proteins, which are intermediary effector proteins
-receptor is a single polypeptide -receptor almost always has seven membrane spanning regions -more than 500 genes encode ligand-gated ion channels -underlie slow synaptic transmission" |
|
|
examples of neurotransmitters for G-protein linked receptors
|
"acetylcholine
GABA glutamate noradrenaline serotonin ATP dopamine neuropeptides" |
|
|
acetylcholine receptor for G-protein linked receptors
|
muscarinic acetylcholine receptor
|
|
|
GABA receptor for G-protein linked receptors
|
GABA_B receptor
|
|
|
glutamate receptor for G-protein linked receptors
|
metabotropic glutamate receptor
|
|
|
noradrenaline receptor for G-protein linked receptors
|
noradrenergic receptor
|
|
|
serotonin receptor for G-protein linked receptors
|
5Ht1 receptor
|
|
|
ATP receptor for G-protein linked receptors
|
P2Y, P2U receptors
|
|
|
dopamine receptor for G-protein linked receptors
|
dopamine receptor
|
|
|
neuropeptides receptor for G-protein linked receptors
|
many different kinds, including substance P, neuropeptide Y, VIP
|
|
|
is there homology between the 2 different families of receptors
|
NO
|
|
|
what does the large size of G protein linked receptors reflect
|
the large number of different neurotransmitters that act through these receptors
|
|
|
mechanism of action for the ligand-gated ion channels
|
ion channel forms an integral part of the receptor
|
|
|
mechanism of action for the G-protein linked receptors
|
the linkage to the effector protein (channel or enzyme) is more convoluted, involving at least one intermediary protein, the G protein
|
|
|
how fast do ligand gated channels open
|
within microseconds of agonist binding
|
|
|
how G-protein linked receptors act
|
in the hundred millisecond to second time frame
|
|
|
what are the 2 different physiological effects ligand gated ion channels can have
|
excitatory or inhibitory
|
|
|
what are excitatory channels selective for
|
cations
|
|
|
what are inhibitory channels selective for
|
anions
|
|
|
which 3 receptors belong to the same gene family and share similar structural features
|
nicotinic acetylcholine, GABA_A, and glycine receptors
|
|
|
when did glutamate receptors arise, where can they be found
|
arose early in evolution, and can be found in single celled bacteria
|
|
|
basic structure of the AChR found at the neuromuscular junction
|
pentamer
|
|
|
how many subunits in AChR
|
4 subunits alpha, beta, gamma, lambda
|
|
|
how many binding sites does AChR have, do they have equal or different affinities for ACh
|
two binding sites, each with diff affinities for ACh
|
|
|
why do AChR binding sites have diff affinities for ACh
|
alpha-subunits are in a non-symmetrical environment surrounded by diff subunits
|
|
|
what is a striking feature of the AChR
|
how much of it projects out of the plane of the cell membrane
|
|
|
how many membrane spanning domains does each subunit of the acetylcholine receptor have, whats it called
|
4 membrane spanning domains named M1 through M4
|
|
|
what are the M2 domains of the AChR important for, why
|
important in determining the ion permeation properties of the channel because of their location (M2 domain lines the inner surface of the channel)
|
|
|
what type of channel is the acetylcholine receptor
|
a cation channel
|
|
|
what does the acetylcholine receptor distinguish between
|
positively and negatively charged ions
|
|
|
what is the main determining factor for the ion selectivity of the pore
|
the charged residues within the channel pore
|
|
|
describe the pore of the AChR
|
there are 3 rings of negatively charged amino acid side chains within the pore which contain 3 or 4 negative charges
|
|
|
what is the purpose of the external and inner rings of the AchR pore
|
they act to decrease the the local concentration of anions around the entrance of the pore
|
|
|
what is the AChR selectivity filter associated with
|
the intermediate ring of negative charges on the cytoplasmic surface of the channel
|
|
|
where is the pore at its narrowest in the open state
|
the intermediate ring region
|
|
|
what does the mechanism of selectivity for the AChR pore involve
|
electrostatic interactions betw. ions and charged side chains
key difference betw. AChR and glycine receptor pore sequences  |
|
|
what residue do all GABA and glycine receptors have
|
proline residue
|
|
|
what do the negative charges in the other rings of the AChR act for
|
to increase the local concentration of cations, which increases the single channel conductance of the channel
|
|
|
where does acetylcholine bind on the receptor
|
to the 2 pockets in the upper part of the receptor
|
|
|
what does binding of ACh induce
|
a conformational change in the receptor that leads to channel opening
|
|
|
what is gating of the AChR channel dependent on
|
the energy associated with ACh binding
|
|
|
what provides the energy for the conformational change that produces gating for voltage gated ion channels
|
changes in the membrane potential
|
|
|
what does ACh binding produce
|
rearrangements in alpha helices surrounding the binding site
|
|
|
when does the AChR open
|
when the M2 helices twist and shift the leucines out of their position blocking the channel, bringing the residues that form the selectivity filter into position to form the lining of the open pore
|
|
|
is there homology betw the amino acid sequence of the glutamate receptors and the AChr/GABAR/GlycineR gene families
|
NO
|
|
|
what do the extracellular regions of the GluR have homology to
|
a bacterial protein that binds the amino acid glutamine
|
|
|
where are the homologous regions in the GluR found
|
in the amino-terminal and the big extracellular loop betw. the M3 and M4 domains
|
|
|
what is the GluR pore design similar to
|
the K+ channel pore
|
|
|
what is the GluR assembled as
|
tetramer, like K+ channel
|
|
|
what is GluR a good example of
|
the modular nature of protein design, with different domains of the protein apparently coming from different original sources
|
|
|
do G-protein linked receptors share a common structure, what is it
|
YES, they have 7 membrane spanning regions and the agonist binding site lies in a deep pocket between the membrane spanning domains
|
|
|
what are virtually all G-protein linked receptors mediated via
|
intermediary proteins known as G-proteins
|
|
|
what are G proteins peripheral membrane
|
proteins located on the intracellular surface of the membrane
|
|
|
how many subunits are G-proteins comprised of
|
3 different subunits
|
|
|
what is the alpha subunit of G proteins
|
GTPase
|
|
|
what is the cycle of G proteins
|
ligand binds to the receptor, the alpha subunit of the G protein releases GDP and binds GTP. Binding of GTP induces a conformational change and the trimeric G-protein separates into 2 parts, the alpha subunit and the beta/gamma subunits. these 2 components can then activate of inhibit effector proteins independently. the cycle ends when the alpha subunit hydrolyzes GTP to GDP and the alpha subunit rebinds to the beta/gamma subunits, thereby inactivating both components of the G-protein
what determines how long the G protein-linked receptor system is turned on for the efficiency of the GTPase |
|
|
effect of a subunit of G-protein
|
can directly activate or inhibit an ion channel or it can activate an enzyme that produces a second messenger that activates a second messenger effector protein, like kinase, that can then modify the function of an ion channel
|
|
|
targets of G proteins
|
activation of G-protein receptors can modulate almost any cellular function
|
|
|
how many synapses are there per cell in the mammalian CNS
|
100 to 100,000
|
|
|
how many synapses are there in human brain
|
10^14 synapses
|
|
|
what is synapse
|
a highly specialized cellular structure that facilitates rapid communication betw. 2 electrically excitable cells
|
|
|
what is the direction of the transfer of electrical excitation
|
from the presynaptic nerve terminal to the post-synaptic cell
|
|
|
what are most synapses
|
chemical synapses-the presynaptic cell releases a signaling molecules known as a neurotransmitter, the neurotransmitter diffuses towards the 2nd cell where it binds to a neurotransmitter receptor. binding of the neurotransmitter then triggers a response in the 2nd cell via activation of the neurotransmitter receptor
|
|
|
what are the functions of the unique geometry of he synapse
|
"1.it reduces diffusion times
2.increases the specificity of signaling" |
|
|
what are diffusion times proportional to
|
the square of the distance over which the molecules diffuse
|
|
|
what is the synapse made by
|
2 cells
|
|
|
what is the nerve terminal filled with
|
small spherical structures known as synaptic vesicles
|
|
|
synaptic vesicles
|
membrane bound spheres that are filled with neurotransmitter
|
|
|
specializations on the surface of the nerve terminal
|
vesicle docking sites of active zones- points where the vesicles bind and then fuse with the cell membrane to release neurotransmitter into the synaptic cleft
|
|
|
where do voltage-gated calcium channels lie
|
in the presynaptic membrane
|
|
|
sequence of events during synaptic transmission at a typical synapse
|
"1.AP travels down axon
2.AP invades the nerve terminal causing depolarization 3.depolarization opens voltage-gated Ca+2 channels 4.influx of Ca+2 ions through the Ca+2 channels raises the Ca+2 conc. inside the nerve terminal 5.inc. in internal Ca conc. promotes the fusion of synaptic vesicles with the cell membrane 6.fusion of synaptic vesicles releases neurotransmitter into synaptic cleft 7.neurotransmitter binds to neurotransmitter receptors in cell membrane of post-synaptic cell 8. binding of neurotransmitter to the receptor induces a conformational change in the receptor that opens an ion channel 9. opening of ion channels produces a synaptic current in the postsynaptic cell 10.the synaptic current produces a change in the membrane potential of the postsynaptic cell, possibly triggering an AP 11.neurotransmitter is removed from the synaptic cleft 12. components of the synaptic vesicles are recycled" |
|
|
what is the nature of the synapses determined by
|
the kind of neurotransmitter that the synapse releases and the type of neurotransmitter receptor found on the postsynaptic membrane
|
|
|
what do excitatory receptors allow for
|
cations to pass through their integral ion channels
|
|
|
excitatory postsynaptic potential (epsp)
|
when the ligand-gated ion channels open and depolarize the cell membrane potential bringing the membrane potential closer to the threshold for AP firing
|
|
|
inhibitory postsynaptic potential (ipsp)
|
activation of inhibitory receptors moves the membrane potential away from the threshold potential
|
|
|
neuromuscular junction
|
synapse betw a motor neuron and a skeletal muscle fiber
|
|
|
who discovered almost everything about synaptic transmission
|
Bernard Katz
|
|
|
what is the neurotransmitter at the neuromuscular junction
|
acetylcholine
|
|
|
what does the active zone of the presynaptic membrane contain
|
voltage-gated Ca+2 channels
|
|
|
contributions of Bernard Katz
|
"-vesicle hypothesis
-Ca hypothesis -2 step kinetic model of AChR activation -kinetic model of AChR desensitization -measurements of single channel conductance and open time using noise analysis" |
|
|
vesicle hypothesis
|
vesicles seen in the electron micrographs were filled with neurotransmitter and the miniature epsp were due to the spontaneous fusion of these vesicles with the membrane
|
|
|
Ca+2 hypothesis
|
Ca ions are the link betw excitation and secretion
synaptic delay time taken between an action potential arriving in the presynaptic nerve and the initiation of the post-synaptic action potential  |
|
|
sources of the synaptic delay
|
"-delay associated with activation of Ca+2 channels (slower kinetics than Na+ channels)
-exocytosis -diffusion -activation of neurotransmitter receptors -charging of membrane capacitance" |
|
|
why is the NMJ "fail safe"
|
cuz the synapse is so large
|
|
|
how big is the epsc underlying the epsp at the NMJ, whats it called
|
3 times larger than needed to cross threshold- safety margin (provides a measure of security at the neuromuscular synapses during stress or disease)
|
|
|
how is neurotransmitter removed from the synaptic cleft
|
by enzyme action, reuptake, diffusion, etc.
|
|
|
acetylcholinesterase
|
enzyme that inactivates ACh at the NMJ
|
|
|
why is the pulse of ACh in the synaptic cleft following a presynaptic action potential quite brief
|
cuz of the rapid action of acetylcholinesterase enzyme
|
|
|
what does acetylcholinesterase split ACh into
|
acetate and choline
|
|
|
how is the membrane in the synaptic vesicles recycled
|
by the process of endocytosis
|
|
|
summation
|
CNS generally requires the coordinated actions of a number of cells acting on the postsynaptic neuron
|
|
|
what types of summation are there
|
temporal and spatial summation between synaptic inputs to bring the membrane potential to threshold
|
|
|
temporal summation
|
summation over time
|
|
|
what does repetitive firing of the same synapse cause
|
the membrane potential to become more depolarized than if the synapse fired more slowly
|
|
|
spatial summation
|
summation of more
than one synaptic input firing simultaneously. |
|
|
what are the receptors at most excitatory receptors in the CNS
|
glutamate receptors
|
|
|
what are the 2 types of important glutamate receptors
|
AMPA and NMDA
|
|
|
genes for AMPA receptors
|
GluR-A, GluR-B, GluR-C, GluR-D
|
|
|
properties of AMPA receptors
|
-main form of GluR
-most native receptors contain the GluR-B subunit -fast kinetics -fast opening, closing, and desensitization -low Ca permeability -small conductance |
|
|
genes for NMDA receptors
|
NR-1, NR-2A, NR-2B, NR-2C, NR-2D
|
|
|
properties of NMDA receptors
|
-all receptors contain the NR-1 subunit, which has the agonist binding sites
-slow kinetics -large single channel conductance -high Ca permeability -channel blocked by Mg ions -glycine is a co-agonist |
|
|
what are the AMPA and NMDA subtypes of glutamate receptors named for
|
because of their sensitivity to artificial agonist and antagonists
|
|
|
agonist for NMDA receptors
|
NMDA
|
|
|
agonist for AMPA receptors
|
AMPA
|
|
|
antagonist for NMDA receptors
|
APV
|
|
|
antagonist for AMPA receptors
|
CNQX
|
|
|
what is an agonist
|
chemical that binds to a receptor of a cell and triggers a response by that cell.
|
|
|
what is an antagonist
|
chemical that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses.
|
|
|
are AMPA and NMDA found at the same excitatory synapse
|
YES
|
|
|
when does long term potentiation occur
|
when excitatory synaptic inputs to a neuron are strongly activated
|
|
|
what does potentiated mean
|
strengthened
|
|
|
what is LTP mediated by
|
Ca ions entering the cell through NMDA receptors
|
|
|
how does influx of Ca affect synaptic connection
|
it leads to strengthening of synaptic connection
|
|
|
what is modulation of the strength of synaptic connections important for
|
development and learning
|
|
|
excitotoxicity
|
nerve terminals depolarize, release glutamate, glutamate activates NMDA receptors and Ca ions flow into postsynaptic neuron. the rise in internal Ca concentrations can kill the postsynaptic cell
|
|
|
primary inhibitory neurotransmitter in the CNS
|
GABA
|
|
|
what is the GABA receptor permeable to, what effect does it have?
|
Cl ions, hyperpolarization
|
|
|
what determines whether or not the cell fires an AP
|
e balance of
excitatory and inhibitory synaptic inputs that the cell is receiving at any particular point in time |
|
|
what is required to make a decision or produce an action.
|
the averages response of multiple neurons
|
|
|
what are slow synaptic inputs mediated by
|
G-protein linked receptors
|
|
|
what did Paul Adams discover
|
that one key target for the muscarinic receptor was a voltage-gated potassium channel called the M-channel
|
|
|
what effect will inhibiting K+ channels have on the neuron
|
it makes the neuron more excitable
|
|
|
what is the response of neurons dependent on
|
both on the nature of the fast synaptic inputs that
it receives and how the excitability has been modulated by prior slow synaptic inputs. |
|
|
schemes for classification of voltage gated ion channels
|
-ion selectivity
-kinetic properties -threshold for activation -subcellular location -pharmacology -gene family |
|
|
what can voltage gated ion channels be selective for
|
Na, K, Ca, or cations
|
|
|
what currents are excitatory and depolarize the cell
|
Na, Ca, and cation currents
|
|
|
what currents will decrease the excitability of the cell and hyper-polarize the membrane potential
|
K currents and Cl currents
|
|
|
kinetic parameters that are most easily observed experimentally
|
activation, deactivation, inactivation, and recovery from inactivation
|
|
|
rapidly activating channels
|
Na channel -I_NA
K channel- I_A (A-type K channel) |
|
|
non-activating channels
|
Na channel-I_Na,P (persistent Na channel)
K channel-I_M (M type K channel) |
|
|
what largely determines the threshold potential
|
properties of the transient Na current (I_Na)
|
|
|
what is often the single largest current in the cell
|
transient Na current (I_Na)
|
|
|
currents devoted to repolarizing the action potential
|
delayed rectifier K current (I_K) and the large Ca activated K (I_C)
|
|
|
what do subthreshold currents do? examples
|
they modulate the cell's response to synaptic currents. the K+ currents I_A, I_D, I_M, I_AHP, the Ca+ current I_T and the cation current I_H
|
|
|
which currents have negative inactivation curve
|
I_T, I_A, I_D
|
|
|
functionally differentiated subcellular compartments of neurons
|
dendrites, soma, axon, nerve terminal, (axon hillock)
|
|
|
simplest compartment of a neuron, what does it express
|
axon; expressing the transient sodium current and a delayed rectifier potassium current
|
|
|
what does the nerve terminal express
|
Ca+ current
|
|
|
what does the lack of selectivity of pharmacological agents reflect
|
the fact that the channel pore is a highly conserved region of the channel
|
|
|
classes of pharmacological agents affecting channel function
|
channel blockers, toxins, allosteric modifiers
|
|
|
what are channel blockers? ex?
|
small molecules that bind to the channel pore and block the passage of ions. ex: TEA, 4-AP,
XE991 |
|
|
what are toxins? ex?
|
neurotoxins from a wide variety of species that bind to ion channels
ex: tetrodotoxin, charybdotoxin, apamin. |
|
|
what are allosteric modifiers? ex?
|
small molecules that bind to the channel outside of the pore region and modify the channel function by modifying the kinetic properties of the channel, making it less or more likely to open
ex: dryhydropyridines |
|
|
what do dihydropyridines modify
|
function of the L-type calcium channel
|
|
|
what are pharmacological agents used for
|
to block channels and classify them
|
|
|
how many families of genes are there? what are they?
|
5- voltage gated Na channels, voltage gated Ca channels, K channels, cyclic nucleotide-modulated channel, transient receptor potential channels
|
|
|
what is the total number of genes in this gene superfamily in mammals
|
143 genes
|
|
|
what is the predominant family of genes
|
K channel subfamily with 78 genes
|
|
|
what are Na and Ca channels restricted to
|
excitable cells
|
|
|
subfamily of voltage gated Na channels and # of genes
|
Na_V, 10
|
|
|
subfamily of voltage gated Ca channels and # of genes
|
Ca_V, 11
|
|
|
subfamilies of potassium channels and # of genes
|
K_V (40), K_Ca (8), K_2P(15), K_ir(15)
|
|
|
subfamilies of cyclic nucleotide-modulated channel and # of genes
|
CNG (6), HCN (4)
|
|
|
subfamilies of transient receptor potential channels and # of genes
|
TRP & relatives (32 genes)
|
|
|
main function of I_Na
|
trigger an AP
|
|
|
how many different members does the sodium channel gene family have? what are they?
|
9 diff members: 1.6,1.2,1.1,1.3,1.7,1.4,1.5,1.8,1.9
|
|
|
what are all sodium channels blocked by
|
the toxin TTX
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which sodium channels are most sensitive
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Na_V 1.1,1.2,1.3,1.7
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threshold of activation for I_Na,P
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-65 mV
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is I_Na,P activating or non-activating current
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relatively rapidly activating that is either non-activating or inactivates only slowly
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what is I_Na,P blocked by
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TTX
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what does I_Na,P do
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makes the cell more
excitable and increases firing frequency |
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role of Calcium channels
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current carriers and indirectly control calcium concentrations by controlling the influx of Ca+2 ions into the cell
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what cellular activities do calcium channels modulate
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neurotransmitter release, hormone release, muscle contraction and regulation of gene expression
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what are the primary characteristics of Ca channels determined by
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alpha subunit
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subfamilies of I_T
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Ca_V 3.1,3.2, 3.3
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I_T
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-transient, low threshold current that activated at about -65mV.
-fast kinetics and activates and inactivates relatively rapidly -steady state inactivation curve |
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subfamilies of I_L
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Ca_V 1.1,1.2,1.3,1.4
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I_L current
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-slowly inactivating high threshold current
-can influence spike repolarization -play an important role in regulation of gene transcription |
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I_N subfamiliy
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Ca_V 2.1
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I_P/Q subfamily
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Ca_V 2.2
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I_R subfamily
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Ca_V 2.3
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I_N, I_P/Q, I_R
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-high threshold, inactivating currents
-contribute to neuronal firing properties -mediate neurotransmitter release |
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where is the greatest diversity of currents found
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for K+ currents
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what roles do K+ currents have
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shaping the response to synaptic input and modifying firing properties
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what are K channels comprised of
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4 subunits and assemble as tetramers
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how many transmembrane domains do K_V channels have
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6 transmembrane spanning domains
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transmembrane domains in K_Ca channel
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7
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structure of inward rectifier channels (K_ir)
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2 transmembrane architecture
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structure of 2 pore channels (K_2P)
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2 pore domains in a single subunit and assemble as dimers
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I_K
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The delayed rectifier current is an extremely heterogeneous current in vivo and the pharmacological
properties of the current show that in neurnons it typically has multiple separate components produced by different channels |
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what is I_K blocked by
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TEA
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does I_K have a high or low threshold
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high threshold typically
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primary function of I_K current
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repolarization of AP
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I_A
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-rapidly activating, rapidly inactivating potassium current
-low threshold -relatively negative steady state inactivation curve |
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what is I_A blocked by
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4- AP
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what does I_Na do in dendrites
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reduces the size of back-propagating AP and reduces the size of epsps
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I_D
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-very negative activation and steady-state inactivation curves
-sensitive to 4-AP -involved in facilitating temporal summation of synaptic inputs |
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I_M
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low threshold, non activating potassium current with very slow activation and deactivation kinetics
-contributor to spike accommodation during prolonged depolarizing current steps -opposes summation of excitatory synaptic inputs |
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I_M
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low threshold, non activating potassium current with very slow activation and deactivation kinetics
-contributor to spike accommodation during prolonged depolarizing current steps -opposes summation of excitatory synaptic inputs |
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I_C
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-activated by both voltage and intracellular calcium
-has relatively high channel conductance |
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what is I_C blocked by
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TEA and charybdotoxin
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primary function of I_C
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repolarization of the action potential and it behaves like a delayed rectifier current
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what is I_AHP activated by
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intracellular calcium
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I_AHP
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-relatively small single channel conductance
-slow kinetics for activation and deactivation -some are sensitive to block by toxin apamin |
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how many membrane spanning domains does I_IR have
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2
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how is gating of I_IR channel accomplished
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via channel block, usually by intracellular Mg+2 ions and polyamines
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what does I_IR channel contribute to
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-the resting membrane potential
-facilitate synaptic transmission |
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who does the I_leak get contributions from
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multiple channel types, predominantly potassium selective.
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what genes are I_H channels encoded by
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HCN1,2,3,4
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is I_H cation or anion selective
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cation selective
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does I_H has fast or slow kinetics
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slow kinetics
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unique feature of I_H channel
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its activated by hyperpolarization and inactivated by depolarization
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Na-Ca exchanger
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uses downhill movement of Na into the cell to pump Ca out by secondary active transport
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what do other transporters linked to Na gradient move
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amino acids from kidney tubules into blood
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what kind of movement allows reuptake of neurotransmitters from synaptic cleft
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secondary active transport
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activation
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channels move from closed to open state
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deactivation
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membrane potential quickly moves back to rest, the channel moves from open to closed state
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inactivation
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if the voltage step to 10mV is maintained for a prolonged period, the channels leave the opens state and become inactivated
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2 ways a channel can inactivate
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N type
C type |
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what is N type inactivation
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a ball (located at amino terminus of protein) blocks conduction through the pore
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what is C type activation
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complex; constriction of the pore
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overshoot
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height of AP above zero
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when does absolute refractory period occur
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during repolarization
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when does relative refractory period occur
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during afterhyperpolarization
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spatial summation
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summation of more than one synaptic input firing simultaneously
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when does long term potentiation occur
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when excitatory synaptic inputs are strongly activated
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excitotoxicity
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cell toxicity thats produced by excitatory neurotransmitter;
stroke->release glutamate->NMDA receptors activate & release Ca->postsynaptic cell dies |
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receptors at most excitatory receptors in CNS
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glutamate receptors; AMPA & NMDA
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primary inhibitory neurotransmitter
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GABA
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describe AMPA receptors
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rapidly activated by glutamate, pass monovalent cations, have a linear Vl with reversal potential around 0mV
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describe NMDA receptors
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activated by both agonist & voltage, Vl curve for NMDA isnt linear cuz Mg ions block the channel
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when does NMDA pass significant current
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at positive potentials
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when does APV have a large effect? on what?
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at 20 mV, NMDA receptor
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pyramidal cells
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single layer of projection neurons on hippocampus
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trisynaptic current
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major pathway through hippocampus
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flow of info in hippocampus
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from the cortex & back to the cortex
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where did they stimulate & record in the experiment of the hippocampus
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stimulated the perforant pathway and recorded from cells in Dentate gyrus
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post-tetanic potentials (PTP)
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occurs when a rapid repeated stimulus (tetanic stimulus) causes transient increase in synaptic strength
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long term potentiation (LTP)
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occurs after PTP, when there's a maintained enchancement
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properties of LTP
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-specificity
-cooperativity -associativity |
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specificity of LTP
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when strong & weak input to same cell arent closely paired in time then only the strong input shows LTP
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cooperativity of LTP
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if only weak input is stimulated, LTP doesnt form
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associativity of LTP
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is a strong input is paired with a weak input, the weak input will show LTP
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what is required for induction of LTP
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post-synaptic depolarization
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hebbian synapses
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requirement of post-synaptic activity in conjuction with presynaptic activity
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what is the NMDA receptor like at resting membrane potential
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it is blocked by Mg
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what must occur for the NMDA receptor to open
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neurotransmitter must bind to the receptor and the cell membrane must be depolarized
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what is the NMDA receptor blocked by
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agonist glutamate & voltage
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how does APV block the LTP
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by blocking Ca influx through the NMDA receptor
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why does specificity occur in LTP
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only strong inputs depolarize the cell enough to relieve Mg block of NMDA receptor and receive Ca influx
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why does cooperativity occur in LTP
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strong synaptic input is required to depolarize the cell and allow Ca influx
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why does associativity occur in LTP
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strong input can depolarize the cell sufficiently to allow Ca influx at the synapses innervated by weak input
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2 kinds of LTP
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associative & non associative
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describe associative LTP
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-NMDA receptor dependent (strong input can result in enhancement of weak input)
-mechanism for encoding associations between temporally correlated events |
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describe non associative LTP
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these synapses have few or no NMDA receptors
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do all 3 synapses in trisynaptic pathway demonstrate LTP
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yes!
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