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376 Cards in this Set

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Proteins that span the entire cell membrane
Integral proteins
Diffusion Equation
J = -PA (C1-C2)
Q: What is the equation for flux through a membrane?
A: J = -PA(C1 - C2)

J = flux, P = permeability, A = area, C = concentration
WHAT IS ANOTHER NAME FOR A TIGHT JUNCTION?
ZONULA OCCLUDENS
What are the components of cell membranes?
Phospholipids and proteins
Membrane proteins that include Ion channels and Transport proteins
Integral proteins
Inhibitors of Na/K/ATPase
Ouabain
Digitalis
Q: What factors increase permeability?
A: 1) Increased oil/water partition coefficient, 2) Decreased radius of the solute, 3) Decreased membrane thickness
SIMPLE DIFFUSION EQUATION
FLUX = (PERMEABILITY)(AREA)(CONC1 - CONC2)

(CONC1 > CONC2, FROM HIGH TO LOW CONC)
What is the structure of a phospholipid?
Two hydrophobic fatty acid tails esterified to a hydrophilic glycerol backbone
Membrane proteins that are located on either the intracellular or extracellular side of the cell
Peripheral proteins
omeprazole
inhibits the H/K/ATPase pump
Q: Can carrier-mediated transporters be stereospecific?
A: Yes. For example, some transporters can transport D-Glucose, but not L-Glucose.
WHAT SOLUTE IS INVOLVED IN COTRANSPORT / SYMPORT?
[NA+] DOWNHILL IN SAME DIRECTION AS SOLUTE
What sorts of substances can dissolve across cell membranes?
Lipid soluble substances (small, uncharged things) such as O2, CO2, and steroid hormones, because can dissolve in the hydrophobic bilayer
Membrane proteins that include Hormone receptors
Peripheral proteins
Example of secondary active transport, cotransport
Na-glucose cotransporter
- found in the luminal membrane of intestinal mucosa
- found in the renal proximal tubule
Q: What inhibits gastric proton pumps?
A: Omeprazole
WHAT SOLUTE IS INVOLVED IN COUNTERTRANSPORT / ANTIPORT?
[NA+] DOWNHILL IN OPPOSITE DIRECTION TO SOLUTE
What sorts of substances cannot dissolve across cell membranes?
Water soluble substances (large or charged things) such as Na+, Cl-, glucose, and H2O because they cannot dissolve in the lipid interior
Zonula occludens alternate name
Tight junction
Example of secondary active transport, coutertransport/exhchange
Na-Ca countertransport
Q: What inhibites Na+,K+-ATPase pumps?
A: Ouabain and digitalis
WHICH IS FASTER?

1)FACILITATED DIFFUSION
2)SIMPLE DIFFUSION
FACILITATED DIFFUSION
How are lipid-insoluble substances transported across cell membranes?
Water-filled channels, pores, protein transporters
Attachments between cells that may be an intercellular pathway for solutes, depending on size, charge, and characteristics of the particular things I'm asking about
Tight jxn (Zonula occludens)
Equation for osmolarity
Osmolarity = g x C
- g = number of particles in solution (osm/mol)
- C = concentrastion (mol/L)
- Osmolarity (osm/L)
Q: What is the equation for osmolarity?
A: g x C

g = number of particles in solution, C = concentration
WHAT DOES A [NA+][K+] ATP-ASE PUMP DO?
3 [NA+] OUT, 2 [K+] IN

(BOTH UPHILL)
What are integral membrane proteins?
Anchored to and embedded in the cell membrane via hydrophobic interactions. They may span the cell membrane
Are attachments between cells that permit intercellular communication
-Example: permit current flow and electrical coupling between Myocardial cells
Gap junctions
Van't Hoff's Law
pi = g x C x RT

- R = 0.082L atm/mol K
Q: What is the definition of osmolarity?
A: The number of osmotically active particles in a solution.
WHAT ARE SOME CARDIAC GLYCOSIDE INHIBITORS OF THE [NA+][K+] ATP-ASE PUMP?
1) OUABAIN
2) DIGITALIS
What are peripheral membrane proteins?
Loosely attached to the cell membrane via electrostatic interactions
Describe the Na+, K+ ATPase pump
-transports 3 Na+ out of cell against its gradient

-transports 2 K+ into the cell against its gradient
What is the reflection coefficient (sigma)?
a number between zero and one that describes the ease with which a solute permeates a membrane
1: solute is impermeable
0: solute is completely permeable
Q: What is the equation for osmotic pressure?
A: π = g x C x RT

g = number of particles in solution, C = concentration, R = gas constant, T = absolute pressure
WHAT IS SERCA?
SARCOPLASMIC RETICULUM AND ER [CA2+] ATP-ASE PUMP

([CA2+] UPHILL)
What are the two major types of intercellular junctions?
Tight junctions (zonula occludens)
Gap junctions
What are 2 drugs that inhibit the Na+/K+ ATPase pump?
Oubain

Digitalis
What is the effective osmotic pressure?
osmotic pressure x reflection coefficient
Q: What is the definition of the reflection coefficient?
A: A number between zero and one that describes the easy with which a solute permeates a membrane. σ = 1 = impermeable. σ = 0 = solute is completely permeable.
Describe the major features of tight junctions
Often found between epithelial cells
May serve as an intercellular pathway for solutes
May be tight (impermeable) or leaky (permeable)
Where is the H+/K+ ATPase at and what does it do?
Gastric Parietal Cells

transports H+ into the stomach lumen against its gradient
define permeability
the probability of a channel being open
Q: What ions are transported by the nicotinic receptor at the NMF?
A: Na+ and K+
WHAT IS A [H+]{K+] ATP-ASE PUMP/PROTON PUMP INHIBITOR?
OMEPRAZOLE
Describe the major features of gap junctions
Exist between cells that require intercellular communication
Permit solute flow and electrical coupling between myocardial cells
What drug inhibits the H+/K+ ATPase (proton pump) in Parietal Cells?
Omeprazole
Nernst Equation
E = -2.3RT/zF log[C_i]/[C_e]

C_i = intracellular concentration
C_e = extracellular concentration
Q: What blocks voltage sensative Na+ channels?
A: Tetrodotoxin (TTX) and lidocaine
WHAT HAPPENS TO SECONDARY ACTIVE TRANSPORT IF PRIMARY ACTIVE TRANSPORT INHIBITED?
INHIBIT PRIMARY ACTIVE TRANSPORT (EG [NA+][K+] ATP-ASE)-> SMALLER [NA+] GRADIENT -> SECONDARY ACTIVE TRANSPORT SLOWS DOWN AS IT RELIES INDIRECTLY ON [NA+] GRADIENT
What is simple diffusion?
Only form of transport that is not carrier-mediated
Occurs down an electrochemical gradient
Does not require energy
Describe the Na+/glucose cotransport system in the intestinal mucosa and renal proximal tubule cells
-works by Secondary Active Transport
-Na+ is pumped out of the cell by the Na+/K+ ATPase
-this creates a downhill gradient for Na+ and glucose to come into the cell
-poisoning the Na+/K+ pump stops the Na+/glucose cotransport
What is the valude of 2.3RT/zF at 37 degrees Celcius (assuming z= 1)
60mV
Q: What does gates does depolarization affect in the nerve action potential?
A: 1) Rapid opening of the activation gates of the Na+ channel, 2) Closes the inactivation gates of the Na+ channel, and 3) Slowly opens repolarization K+ channels
OSMOLARITY EQUATION
OSMOLARITY = (NUMBER OF PARTICLES IN SOLUTION)(CONC)

(EG NA-CL = 2 PARTICLES IN SOLUTION; GLUCOSE = 1)
What is the formula for flux/diffusion?
J = -PA(C1 - C2)
J = flux
P = permeability
A = area
C = concentration
The flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration
Osmosis
E for Na
65mV (inside of cell positive at equilibrium)
Q: What is responsible for the absolute refractory period of the nerve action potential?
A: Closing of the inactivation gates of the voltage-gated Na+ channel.
COLLOIDOSMOTIC PRESSURE / ONCOTIC PRESSURE
PRESSURE DUE TO PRESENCE OF PROTEINS (EG PLASMA PROTEINS)
What is "permeability?"
It describes the ease with which a solute diffuses through a membrane. It depends upon the characteristics of the solute and the membrane
When does Osmotic Pressure increase?
when the solute concentration increases
E for Ca
120 mV (inside of cell is positive at equilibrium)
Q: What is responsible for the relative refractory period of the nerve action potential?
A: Hyperpolarization that results from increased K+ permeability when the repolarizing K+ channels open.
REFLECTION COEFFICIENT
EASE WITH WHICH A SOLUTE PERMEATES A MEMBRANE

(1 = IMPERMEABLE, 0 = COMPLETELY PERMEABLE)
What are some factors that increase permeability of a solute in a membrane?
A high oil/water partition coefficient (increases lipid solubility)
Low radius of the solute (increases speed of diffusion)
Low membrane thickness (decreases the diffusion distance)
Which has a higher Osmotic pressure: 1 M CaCl2 or 1 M KCl?
1 M of CaCl2 b/c it has 3 particles compared to 2
E for K
-85mV (inside of cell is negative at equilibrium)
Q: What is accommodation in nerve action potentials?
A: Occurs when cell membrane is held at a depolarized level for extended periods, such that the threshold is passed without firing an action potential. Closes the inactivation gates of the Na+ channel. Demonstrated in hyperkalemia.
SERUM ALBUMIN REFLECTION COEFFICIENT
NEARLY 1 B/C LARGE SOLUTE THAT IS NOT PERMEABLE (EXERTS NEARLY MAXIMAL OSMOTIC PRESSURE)
What types of molecules have the highest permeabilities in lipid membranes?
Small, hydrophobic solutes
Is the concentration of osmotically active particles in a solution
Osmolarity
E for Cl
-85 mV (insde of cell is negative at equilibrium)
Q: What catalyzes the formation of ACh?
A: Choline acetyltransferase.
UREA REFLECTION COEFFICIENT
NEARLY 0 B/C SMALL SOLUTE THAT IS EASILY PERMEABLE (EXERTS ALMOST NO OSMOTIC PRESSURE)
How does facilitated diffusion differ from simple diffusion?
Requires a carrier protein, and is therefore more rapid
What is the osmolarity of 1 M NaCl?
2 particles X 1 M = 2 osm/L
Define resting membrane potential
the intracellular potentail relative to the extracellular potential.

e.g. -70mV = 70mV, cell negativeg
Q: How is ACh removed from the NMJ?
A: Degraded by AChE. Note: 1/2 of choline is taken back into the presynaptic ending by Na+-choline cotransport and used to synthesize new ACh.
WHAT IS AN EQUILIBRIUM POTENTIAL?
AN EQUILIBRIUM POTENTIAL COUNTERACTS AGAINST A SOLUTE'S CHEMICAL GRADIENT -> WHEN BALANCED = ELECTROCHEMICAL EQUILIBRIUM
What does it mean for a membrane carrier protein to exhibit stereospecificity?
It distinguishes between D- and L- enantiomers
If the Reflection Coefficient is 1, the solute is _______.

What is an example?
Impermeable

Albumin
Define inward current
postive charge flowing into the cell
Q: Where is NE primarily released?
A: Postganglionic sympathetic neurons
[NA+]EQUILIBRIUM POTENTIAL IN NERVE AND MUSCLE
+65 mV
What does it mean for a membrane carrier protein to exhibit saturation?
The transport rate increases as solute concentration increases, until the carriers are saturated (ie when you reach the transport maximum Tm)
If the Reflection coefficient is 0, the solute is ______

What is an example?
completely permeable

Urea = does not exert any osmotic effect
What can block voltage-sensitive Na channels and prevent action potentials?
Tetrodotoxin
Lidocaines
Q: How is NE removed from the synapse?
A: Reuptake or is metabolized by MAO (monoamine oxidase) and COMT (catechol-O-methyltransferase)
[CA2+]EQUILIBRIUM POTENTIAL IN NERVE AND MUSCLE
+120 mV
What does it mean for a membrane carrier protein to exhibit competition?
Structurally related solutes may compete for transport sites (ie galactose is a competitive inhibitor of glucose transport in the small intestine)
What sort of transport is used to transport glucose into muscle and adipose tissue?
Facilitated diffusion
What current causes depolarization?
inward Na current
Q: What is neostigmine?
A: A AChE inhibitor
[K+]EQUILIBRIUM POTENTIAL IN NERVE AND MUSCLE
-85 mV
What happens to glucose uptake in diabetes mellitus?
Glucose uptake by muscle and adipose tissue is inhibited because the carriers require insulin
What current causes repolarization?
outward K current
Q: What is hemicholinium?
A: Blocker of choline reuptake, which depletes neural presynaptic terminals of ACh stores.
[CL-]EQUILIBRIUM POTENTIAL IN NERVE AND MUSCLE
-85 mV
What are the features of primary active transport?
Occurs against an electrochemical gradient
Requires direct energy input (ATP)
Carrier-mediated
What is accommodation?
cell membrane is held at depolarized level even with the threshold potential is passed.
e.g. hyperkalemia: skeletal muscle membranes are depolarized by high serum K+
Q: How is epinephrine synthesized?
A: It is synthesized from NE via POMNT in the adrenal medulla.
ERNST EQUATION
EQUILIBRIUM POTENTIAL = [(-60 mV AT 37 DEGREES CELSIUS)/Z] LOG10 (CONC INTRACELLULAR / CONC EXTRACELLULAR)

Z = CHARGE OF ION
What type of transport does the Na-K pump use?
Primary active transport
What catalyzes the formation of ACh from acetyl coenzymeA (CoA) and choline?
Choline acetyltransferase
Q: Where is dopamine prominently found?
A: Midbrain neurons
RESTING MEMBRANE POTENTIAL ALWAYS REPORTED AS INTRACELLULAR TO EXTRACELLULAR
-70 mV MEANS THAT THE CELL IS 70 mV NEGATIVE
What does the Na-K pump do?
Transports 3 Na into the cell and 2 K out of the cell. Both ions are transported against their gradients.
What are proteoglycans?
Proteoglycans are a major component of the animal extracellular matrix, the 'filler' substance existing between cells in an organism. Here they form large complexes, both to other proteoglycans, to hyaluronan and to fibrous matrix proteins (such as collagen). They are also involved in binding cations (such as sodium, potassium and calcium) and water, and also regulating the movement of molecules through the matrix.
Q: How is dopamine metabolized?
A: MOA and COMT
RESTING MEMBRANE POTENTIAL USU -70 mV, CLOSER TO [K+] EQUILIBRIUM POTENTIAL THAN [NA+] EQUILIBRIUM POTENTIAL
AT REST -> NERVE MEMBRANE FAR MORE PERMEABLE TO [K+] THAN [NA+]
What drugs inhibit the Na-K pump?
Ouabain
Digitalis
What is Lambert-Eaton myasthenic syndrome?
patients have antibodies against Ca channels in motor nerve terminals --> less Ca enters nerve termianl and patients have musclar weakness and diminished stretch reflexes
Q: What are the dopamine receptors?
A: D1, which activates Gs protein, and D2, which actives Gi protein
WHAT CAN BLOCK INWARD [NA+] CHANNELS AND CAN PREVENT AN AP?
1) TETRODOTOXIN (TTX)
2) LIDOCAINE
What type of transport does the Ca pump use?
Primary active transport
Where does ACh bind on the nicotinic receptor? What happens after it binds?
Binds to the alpha- subunit --> conformational changge --> central core increases channel conductance to K and Na.
Q: What neurons are degraded in Parkinson's disease?
A: Dopaminergic neurons that use the D2 receptor
ACCOMMODATION
CELL MEMBRANE HELD IN DEPOLARIZED STATE ABOVE THRESHOLD, BUT DOES NOT FIRE OFF AN AP -> B/C [NA+] INACTIVATION GATE CLOSED BY DEPOLARIZATION
What does the Ca ATPase do?
Transports Ca in the sarcoplasmic reticulum or cell membrane. Note that in the SR, this pump is known as SERCA
What does Botulinus Toxin do?
Bockes release of ACh from presynaptic terminals
Q: What receptors are elevated in Schizophrenia?
A: Dopamine D2 receptors
HYPERKALEMIA AND ACCOMMODATION
HIGH SERUM [K+] -> SKELETAL MUSCLE MEMBRANE DEPOLARIZED, BUT [NA+] INACTIVATION GATE CLOSED -> MUSCLE WEAKNESS AND NO AP
What type of transport does the H-K ATPase use?
Primary active transport
What does Curare do?
Competes with ACh for receptors on motor end plate.
Is a type of alpha toxin, since it binds to the alpha subunit on the nicotinic receptor
Q: Where is serotonin primarily found?
A: Brain stem
HOW TO INCREASE CONDUCTION VELOCITY DOWN A NERVE FIBER
A) INCREASE FIBER SIZE -> LESS RESISTANCE
B) MYELINATION
What does the H-K ATPase do?
Allows the gastric parietal cells to transport H into the stomach lumen
What does Neostigmine do?
Inhibits acetylcholinesterase
Q: What is serotonin synthesized from?
A: Tyrosine
WHAT IS THE NEUROMUSCULAR JUNCTION PRE SYNAPTIC NT? BINDS TO WHAT POST SYNAPTIC RECEPTOR?
A) ACH
B) BINDS TO ALPHA UNIT OF A NICOTINIC RECEPTOR, PERMEABLE TO BOTH INWARD [NA+] AND OUTWARD [K+]
What drug inhibits the H-K ATPase?
Omeprazole
What does Hemicholinium do?
Blocks reuptake of choline into presynaptic terminal
Q: Where is histamine primarily found?
A: Hypothalamus
WHAT DOES CHOLINE ACETYLTRANSFERASE DO?
CATALYZES ACETYL COA + CHOLINE -> ACH IN PRE SYNAPTIC TERMINAL
What are the features of secondary active transport?
The transport of at least two solutes is coupled
One solute is transported downhill and provides energy for the uphill transport of the other solute (the energy comes from the concentration gradient, not ATP)
What is a miniature end plate potential (MEPP)?
the smallest possible EPP, resulting fromt he contents from one synaptic vesicle
Q: What are the different types of glutamate receptors?
A: 3 subtypes of ionotropic receptors or "ligand-gated ion channels" (including NMDA) and 1 subtype of metabotropic receptor (which is coupled to a G protein)
WHAT DOES BOTULINUS TOXIN DO?
BLOCKS ACH RELEASE FROM PRE SYNAPTIC -> ABSOLUTELY NO NEUROMUSCULAR TRANSMISSION
What are the two types of secondary active transport?
Cotransport/symport -- the solutes move in the same direction across the cell membrane
Countertransport/antiport -- the solutes move in opposite directions
What is myasthenia gravis
antibodies to the ACh receptor
- skeletal muscle weakness and fatigue
- decreases the size of the EPP
- can be treated by AChE inhibitors
Q: How do the two different GABA receptors work?
A: GABAa receptor increases Cl- conductance and GABAb increases K+ conducance
WHAT DOES CURARE DO?
COMPETES W/ ACH FOR MOTOR END PLATE RECEPTORS -> SMALLER EPP -> MAXIMAL DOSE PARALYZES RESPIRATORY MUSCLES -> DEATH

(EPP = END PLATE POTENTIAL)
WHAT DOES NEOSTIGMINE DO?
INHIBITS ACHESTERASE ->
PROLONGS AND ENHANCES EFFECT OF ACH AT MUSCLE END PLATE
What type of transport is used by the Na-glucose cotransporter in the small intestine?
Symport
Define threshold
inward Na current exceeds outward K current
Q: What are the different bands/lines found in myofibrils?
WHAT DOES HEMICHOLINIUM DO?
PREVENTS REUPTAKE OF CHOLINE INTO PRE SYNAPTIC TERMINAL -> DEPLETES ACH STORES IN PRE SYNAPTIC TERMINAL
What type of transport is used by the Na-K-2Cl cotransporter in the renal thick ascending limb?
Symport
List the excitatory neurotransmitters
Ach, norepi, epi, dopamine, glutamate, serotonin
Q: What are the three globular proteins of troponin?
A: Troponin T (binds to tropomyosin), troponin I (inhibits interaction of actin/myosin), and troponin C (binds Ca2+).
WHAT DOES ACHESTERASE DO?
DEGRADES ACH INTO ACETYL COA + CHOLINE ON MUSCLE END PLATE -> 1/2 CHOLINE REUPTAKE VIA [NA+]-CHOLINE COTRANSPORT AT PRE SYNAPTIC TERMINAL
What type of transport is used by the Na-Ca transporter?
Antiport
List the inhibitory neurotransmitters
GABA, glycine
Q: Where are T tubules located?
A: At the junction of A and I bands.
WHAT IS MYASTHENIA GRAVIS? TX?
AUTOIMMUNE AGAINST ACH RECEPTOR -> FEWER RECEPTORS -> SMALLER EPP + MORE DIFFICULT TO GENERATE AP -> SKELETAL MUSCLE WEAKNESS + FATIGUE

(TX W/ ACHESTERASE INHIBITORS -> PROLONGS ACH EFFECT AT MUSCLE END PLATE + SLOWS DOWN DEGRADATION)
What type of transporter is used by the Na-H transporter?
Antiport
Where does NorEpi bind?
the alpha and beta receptors on the postsynaptic membrane
Q: What are the steps of excitation-contraction coupling?
A: Action potential --> depolarization of T tubules --> conformation change in dihydropyridine receptor --> opens Ca2+ release channels (ryanodine receptors) in SR --> release of Ca2+ into intracellular fluid --> Ca2+ binds troponin C --> conformational change in troponin --> troponin moves tropomyosin out of the way --> cross-bridge cycling
EXCITATORY NT
1) ACH
2) NOREPINEPHRINE (NE)
3) EPINEPHRINE (EPI)
4) DOPAMINE
5) GLUTAMATE
6) SEROTONIN
Describe how Na-glucose cotransport works (give details)
This transporter is in the luminal membrane of the intestinal mucosal and renal proximal tubule cells
Glucose is transported uphill and Na is transported downhill
Energy comes from the downhill Na transport
The Na gradient is maintained by the Na-K pump in the basolateral membrane, so poisoning this pump decreases the Na gradient and its coupled glucose transport
how is Norepi removed from the synapse?
-reuptake
-metabolized by monoamine oxidase (MAO) and catechol-O-methyltrasferase (COMT)
INHIBITORY NT
1) GABA
2) GLYCINE
Describe how Na-Ca transport works (give details)
Transports Ca uphill out of the cell and Na downhill into the cell
Energy comes from the downhill movement of Na, which is maintained by the Na-K pump
Therefore, poisoning the Na-K pump would abolish Na-Ca antiport
What are the metabolites from Norepi metabolism?
- DOMA
- NMN
- MOPEG
- VMA
WHAT CHANNELS ARE OPENED DURING AN EPSP?
CHANNELS PERMEABLE TO BOTH [NA+] AND [K+] -> MEMBRANE DEPOLARIZES TO HALF WAY BTW 2 SOLUTES
What is osmolarity?
The concentration of osmotically active particles in a solution
What happens during pheochromocytoma?
it is a tumor of the adrenal medulla --> secretion of catecholamines --> increased urinary secretion of VMA (vanillylmandelic acid)
WHAT CHANNELS ARE OPENED DURING AN IPSP?
[CL-] CHANNELS -> MEMBRANE HYPERPOLARIZES TO [CL-] EQUILIBRIUM POTENTIAL
What does it mean for osmolarity to be a colligative property?
Can be measured by freezing point depression
Where is Dopamine primarily found?
midbrain
WHAT IS THE SYNTHETIC PATHWAY FOR DOPAMINE, NE, EPI? ENZYMES?
TYROSINE -> L-DOPA -> DOPAMINE -> NE -> EPI

1) TYROSINE HYDROXYLASE
2) DOPA DECARBOXYLASE
3) DOPAMINE BETA-HYDROXYLASE
4) S-ADENOSYLMETHIONINE
What is the equation for osmolarity?
Osmolarity = # particles in solution x concentration
(# of particles in solution is the number that the compound dissolves into in water, so for NaCl, you would use 2, 1 for glucose, etc)
Where is Dopamine secreted?
hypothalamus. Inhibits prolactin secretion.
in this context, it is called prolactin-inhibiting factor (PIF)
1) WHAT IS NE'S SIGNIFICANCE?
2) WHAT SECRETES NE?
3) WHERE IS NE SYNTHESIZED? WHAT TYPE OF RECEPTORS DOES IT BIND TO?
1) PRIMARY NT OF POSTGANGLIONIC SANS
2) ADRENAL MEDULLA SECRETES
3) SYNTHESIZED IN NERVE TERMINAL + RELEASED TO BIND TO ALPHA / BETA RECEPTORS ON POST SYNAPTIC MEMBRANE
What is osmosis?
The flow of water across a semipermeable membrane from low solute concentration to high solute concentration.
How is dopamine metabolized?
by MAO
and COMT
ROLE OF MAO + COMT
METABOLIZE DOPAMINE, NE, + EPI IN PRE SYNAPTIC TERMINAL
What is osmotic pressure?
The extent to which a compartment attracts water into it by having a high solute concentration. Note that this osmolarity is for osmotically active particles only.
What do D1 receptors activate?
adenylate cyclase via Gs protein
METABOLITES OF MAO + COMT
1) DOMA
2) NMN
3) MOPEG
4) VANILLYMANDELIC ACID (VMA)
What is the formula for osmotic pressure?
Osmotic pressure = g x C x RT
g = # osmotically active particles (NaCl = 2, glucose = 1)
C = conc
R = constant (0.82)
T = temp
What do D2 receptors do?
inhibit adenylate cyclase via Gi protein
WHAT IS PHEOCHROMOCYTOMA?
ADRENAL MEDULLA TUMOR -> SECRETES CATECHOLAMINES + INCREASED VMA IN URINE
What does it mean when two solutions are isotonic?
They have the same effective osmotic pressure, so no water would flow across a semipermeable membrane separating them
What happens in parkinsons?
degeneration of dopaminergic neurons that use the D2 receptor --> increase activation of adenylate cyclase via Gi protein
WHERE IS EPI SECRETED?
ADRENAL MEDULLA
What does it mean when a solution is hypertonic or hypotonic to another?
The hypertonic solution has a higher osmotic pressure than the hypotonic solution
What happens in schizophrenia?
increased levels of D2 receptors --> increased inhibition of adenylate cyclase via Gi protein
1) WHERE IS DOPAMINE PROMINENT?
2) WHAT SECRETES DOPAMINE? WHAT DOES DOPAMINE DO IN THIS CASE?
1) PROMINENT IN MIDBRAIN
2) HYPOTHALAMUS RELEASES -> INHIBITS PROLACTIN SECRETION AS PIF
(PROLACTIN-INHIBITING FACTOR)
What is colloid osmotic pressure?
Also known as oncotic pressure
It is the osmotic pressure generated by proteins
Where is seratonin found?
brainstem
1) WHAT DO D1 RECEPTORS DO?
2) WHAT DO D2 RECEPTORS DO?

(DOPAMINE RECEPTORS)
1) D1 ACTIVATE ADENYLATE CYCLASE VIA Gs PROTEIN

2) D2 INACTIVATE ADENYLATE CYCLASE VIA Gi PROTEIN
What is the reflection coefficient?
A number between 0 and 1 that describes the ease with which a solute permeates a membrane
How is seratonin formed?
from tryptophan
WHAT IS PARKINSON'S DISEASE?
DEGENERATION OF DOPAMINERGIC NEURONS USING D2 RECEPTORS
What does it mean if the reflection coefficient is 1?
The solute is impermeable, and is therefore retained in the original solution, where it creates osmotic pressure and causes water flow. Serum albumin is an example of a substance with a reflection coefficient of 1
What is serotonin converted to, and where?
to melatonin by the pineal gland
WHAT HAPPENS TO D2 RECEPTORS IN SCHIZOPHRENIA?
INVOLVES INCREASED LEVELS OF D2 RECEPTORS
What does it mean if the reflection coefficient is 0?
The solute is completely permeable, so it does not exert any osmotic effect and does not cause water flow. Urea has a reflection coefficient close to 0
What is histamine formed from?
histadine
1) WHERE IS SEROTONIN PROMINENT?
2) WHAT IS SEROTONIN'S PRECURSOR?
3) WHAT IS SEROTONIN CONVERTED TO IN THE PINEAL GLAND?
1) PROMINENT IN BRAIN STEM
2) TRYPTOPHAN PRECURSOR
3) CONVERTED TO MELATONIN
Formula for the effective osmotic pressure
Effective osmotic pressure = osmotic pressure x reflection coefficient
Where is histamine found?
hypothalamus
ROLE OF HISTAMINE
1) HISTAMINE PRECURSOR
2) HYPOTHALAMUS
Are ion channels integral or peripheral membrane proteins?
Integral; when they are open, they permit the passage of certain ions
What are the four subtypes of glutamate receptors?
3 are inootropic receptors (ligand gated ion channels; e.g. NMDA)
1 is a metabotropic receptor (coupled to ion channels)
ROLE OF GLUTAMATE
MOST PREVALENT EXCITATORY NT IN BRAIN
How do ion channels exhibit selectivity?
They permit the passage of some ions but not others. Selectivity is based on the size of the channel and the distribution of charges lining it
How is GABA synthesized?
from glutamate by glutamate decarboxylase
Note: GABA is inhibitory while glutamate is excitatory
GLUTAMATE RECEPTOR TYPES
1) IONOTROPIC -> LIGAND-GATED CHANNEL (EG NMDA RECEPTOR)
2) METABOTROPIC -> COUPLED TO ION CHANNEL VIA HETEROTRIMERIC G PROTEIN
What does it mean for an ion channel to be permeable?
They are either open or closed. The conductance of a channel depends upon the probability that they channel is open. The higher the probability of being open, the higher the conductance or permeability
What are the two GABA receptors?
GABA_A: increases Cl conductance
(site of action for benzodiasepines and barbiturates)
GABA_B: increases K+ conductance
ROLE OF GABA
1) INHIBITORY
2) GLUTAMATE PRECURSOR (VIA GLUTAMATE DECARBOXYLASE)
How is the conductance of an ion channel regulated?
The opening and closing of channels is controlled by gates
Where is glycine found?
spinal cord and brain stem
ROLE OF GLYCINE
1) INHIBITORY NT IN SPINAL CORD + BRAIN STEM
2) INCREASES [CL-] CONDUCTANCE
What does it mean for an ion channel to be voltage-gated?
The channel is opened or closed by changes in membrane potential
What does glycine do?
increases Cl conductance
ROLE OF NO
1) SHORT-TERM INHIBITORY NT IN GI, BLOOD VESSELS, + CNS
2) ARGININE -> NO + CITRULLINE (VIA NO SYNTHASE IN PRE SYNAPTIC)
3) SMOOTH MUSCLE SIGNAL TRANSDUCTION VIA GUANYLATE CYCLASE
How is the activity of the Na channel in nerves regulated?
This channel is voltage-gated
The activation gate is opened by depolarization; Na passes through
The inactivation gate is closed by depolarization; Na cannot pass
Where is NO found?
inhibitory neurotransmitter fond in GI tract, blood vessels, and CNS
ROLE OF THICK FILAMENT
1) "A" BAND AT SARCOMERE CENTER
2) CONTAIN MYOSIN -> HEADS BIND ATP + ACTIN

(MYOSIN = 6 POLYPEPTIDES -> 1 PAIR OF HEAVY + 2 PAIRS OF LIGHT CHAINS)
What does it mean for an ion channel to be ligand-gated?
The channel is opened or closed by hormones, second messengers, or neurotransmitters
How is NO synthesized?
Synthesized in presynaptic nerve terminals
NO synthase converts arginine to citrulline and NO
ROLE OF THIN FILAMENT
1) "I" BAND + INTERDIGITATE W/ THICK FILAMENTS
2) CONTAIN ACTIN, TROPOMYOSIN, + TROPONIN
How is the opening and closing of the nicotinic ACh receptor at the motor end plate regulated?
It is a ligand-gated channel
When ACh binds, it opens and is permeable to Na and K, causing depolarization
ROLE OF TROPONIN
REGULATORY PROTEIN THAT PERMITS CROSS-BRIDGE FORMATION WHEN BOUND TO CA2+
What is a diffusion potential?
The potential difference generated across a membrane because of a concentration difference of an ion. This type of potential can only be generated if the membrane is permeable to the ion
What is NO's role in signal transduction?
signal transduction of guanyl cyclase in tissues such as vascular smooth muscle
TROPONIN PROTEIN COMPLEX
1) TROPONIN T -> TROPOMYOSIN ATTACHEMENT W/ TROPONIN
2) TROPONIN I -> INHIBITS INTERACTION BTW ACTIN + MYOSIN
3) TROPONIN C -> CA2+ BINDING -> PERMITS CROSS-BRIDGE WHEN BOUND
What determines the size of a diffusion potential?
The size of the concentration gradient. Note that since diffusion potentials are created by the diffusion of very few ions, there is no real effective change in concentration of the diffusing ions on either side of the membrane
Describe the structure of a muscle fiber
- bundle of myofibrils surrounded by the SR and invaginated by T tubules
T TUBULE
1) CARRY DEPOLARIZATION FROM SARCOLEMMAL MEMBRANE TO CELL INTERIOR
2) FOUND AT A-I BAND JUNCTION
What determines the sign of a diffusion potential?
Whether the diffusing ion is positively or negatively charged
Describe the muscle thick filament
- Found in the A band
- contain myosin
DIHYDROPYRIDINE RECEPTOR
VOLTAGE-SENSITIVE PROTEIN IN T TUBULES THAT CHANGES CONFORMATION WHEN DEPOLARIZED -> OPENS RYANODINE RECEPTORS IN SARCOPLASMIC RETICULUM
What is an equilibrium potential?
The diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a concentration difference
Describe the muscle thin filament
- anchored at the Z lines
- found in the I bands
- contain actin, tropomyosin, and troponin
SARCOPLASMIC RETICULUM
1) SITE OF CA2+ STORAGE + RELEASE FOR EXCITATION-CONTRACTION COUPLING
2) FORMS TRIAD W/ ITS TERMINAL CISTERNAE + T TUBULES
3) MAINTAINS LOW INTRACELLULAR CA2+ VIA SERCA PUMP INTO SR INTERIOR
What is electrochemical equilibrium?
The chemical and electrical driving forces acting upon an ion are equal and opposite, so there is no net diffusion of the ion
What is troponin?
the regulatory protein that allows cross-bridge fomration when it binds to Ca2+
CALSEQUESTRIN
CA2+ BINDING PROTEIN IN SARCOPLASMIC RETICULUM
What is the Nernst equation used for?
Calculation of the equilibrium potential at a given concentration difference for a permeable ion across a cell membrane. It tells us what potential would balance the tendency for diffusion, or the potential at which the ion would be at electrochemical equilibrium
What are the three proteins in Troponin?
- Troponin T: attaches the torponin complex to tropomyosin
- Troponin I: inhibits the interaction fo actin and myosin
- Troponin C: Ca-binding protein that allows actin to bind to myosin whne bound to Ca2+
RYANODINE RECEPTOR
CA2+ RELEASE CHANNEL ON SARCOSPLAMIC RETICULUM
Formula for the Nernst equation
E = -2.3 (RT/zF)log(Cinside/Coutside)
where 2.3(RT/zF) = 60 mV
Where are the t-tubules located?
the junctions of A Bands and I Bands
EXCITATION-CONTRACTION COUPLING
1) AP DEPOLARIZES T TUBULE
2) CA2+ RELEASE INTO INTRACELLULAR FLUID AFTER DIHYDROPYRIDINE RECEPTORS OPEN RYANODINE RECEPTORS ON SR
3) CA2+ BINDS TO TROPONIN C + MOVES TROPOMYOSIN OUT OF THE WAY
4) CROSS-BRIDGE CYCLE BEGINS
What is Ena?
+65 mV
How are T tubules regulated?
have a voltage sensitive protein called the dihydropyridine receptor. Depolarization causes a confromational change in the receptor.
CROSS-BRIDGE CYCLE
1) MYOSIN ATTACHED TO ACTIN, NO ATP BOUND
2) ATP BINDS -> MYOSIN RELEASES FROM ACTIN
3) MYOSIN PUSHED TO + END OF ACTIN -> ATP CLEAVED INTO ADP + Pi
4) POWER STROKE -> MYSOSIN REATTACHED TO ACTIN -> ADP RELEASED
5) CYCLE REPEATS AS LONG AS CA2+ BOUND TO TROPONIN C
What is Eca?
+120 mV
Describe the protein found in T tubules
DHPR: Dihydorpyridine receptor. It interacts with the ryanodine receptor (RYR). When Ca is released from the terminal cisternae fo the SR, a conformational change takes place at the DHRP and this opens the RYR, releasing Ca into the myoplasm
RIGOR
NO ATP PRESENT AND MYOSIN PERMANENTLY BOUND TO ACTIN
What is Ek?
-85 mV
What two other proteins are found near the RYR?
1. Triadin: involved in RYR interaction with DHPR
2. Calsequestrin: low-affinitiy Ca binding protein taht allows Ca to be stored at high concnetration --> makes a concentration gradient that facilitates the efflux fo Ca from the SR into the myoplasm when the RYR opens
TETANUS
INABILITY OF MUSCLES TO RELAX DUE TO PROLONGED RAISED INTRACELLULAR CA2+ -> CROSS-BRIDGE CYCLES CONTINUE
What is Ecl?
-85 mV
Define isometric contraction
length is held constant. No muscle shortening
ISOMETRIC CONTRACTIONS
MUSCLE LENGTH FIXED (AKA PRELOAD) -> CONTRACTION STIMULATED -> TENSION MEASURED

(NO SHORTENING)
What is the resting membrane potential?
The overall membrane potential that is established by diffusion potentials resulting from concentration gradients of all permeant ions. By convention, it is expressed as the intracellular potential relative to the outside, so -70 mV means 70 mV, cell negative
Isotonic contraction
Load is held constant. Shortening of muscle
ISOTONIC CONTRACTIONS
LOAD FIXED (AKA AFTERLOAD) -> CONTRACTION STIMULATED -> SHORTENING MEASURED
What determines which ions contribute the most to the resting membrane potential
The ions with the highest permeabilities make the largest contributions
Why doesn't smooth muscle appear striated?
it's thick and thin filaments are not arranged in sarcomeres.
LENGTH-TENSION RELATIONSHIP
1) MEASURES TENSION DURING ISOMETRIC CONTRACTIONS
2) TOTAL TENSION = PASSIVE + ACTIVE TENSION
3) PASSIVE = TENSION BY STRETCHING MUSCLE TO DIFFERENT LENGTHS
4) ACTIVE = ACTIVE FORCE GENERATED AFTER MUSCLE CONTRACTS
5) ACTIVE TENSION PROPORTIONAL TO NUMBER OF CROSS BRIDGES FORMED -> MAX AT GREATEST OVERLAP BTW THIN + THICK FILAMENTS
6) TOO MUCH STRETCH = TOO LITTLE OVERLAP
7) TOO LITTLE STRETCH = THIN FILAMENTS COLLIDE TOGETHER
8) MUSCLE LENGTH AT WHICH GREATEST OVERLAP = GREATEST ACTIVE TENSION (ACTIVE = TOTAL - PASSIVE)
At rest, what ion is the principal determinant of the resting membrane potential of the nerve?
K
What innervates arterial smooth muscle?
Sympathetics
FORCE-VELOCITY RELATIONSHIP
MEASURES VELOCITY OF SHORTENING DURING ISOTONIC CONTRACTIONS AGAINST DIFFERENT LOADS -> VELOCITY OF SHORTENING DECREASES AS AFTERLOAD INCREASES
How does the Na-K pump contribute to the resting membrane potential?
Only indirectly, by maintaining the Ha and K concentration gradients
Contrast contraction regulation in skeletal and smooth muscle
Skeletal m: increase in intracellular Ca affects actin
Smooth m: increase in intracellular Ca affects myosin
MULTI-UNIT SMOOTH MUSCLE
1) IRIS
2) CILIARY MUSCLE OF LENS
3) VAS DEFERENS

(ACT AS SEPARATE UNITS -> LITTLE TO NO ELECTRICAL COUPLING BTW CELLS)
(DENSELY INNERVATED)
What is depolarization?
When the membrane becomes less negative (the cell interior becomes less negative)
where do you find multi-unit smooth muscle?
iris, ciliary muscle of the lens, and vas deferens
UNITARY / SINGLE-UNIT SMOOTH MUSCLE
1) UTERUS
2) GI TRACT
3) URETER
4) BLADDER

(SLOW WAVES -> SPONTANEOUSLY ACTIVE LIKE A PACEMAKER)
(HIGH DEGREE OF ELECTRICAL COUPLING -> FUNCTION AS A UNIT)
What is hyperpolarization?
When the membrane becomes more negative (the cell interior becomes more negative)
where do you find unitary smooth muscle?
uterus, GI tract, ureter, and bladder
EXCITATION-CONTRACTION COUPLING -> SMOOTH MUSCLE
NO TROPONIN -> CA2+ CONTROLLED

1) DEPOLARIZATION OPENS INWARD CA2+ CHANNELS
2) ENTERING CA2+ CAUSES MORE CA2+ RELEASE FROM SR AND HORMONES/TRANSMITTERS OPEN MORE IP3-GATED CA2+ CHANNELS
3) INTRACELLULAR CA2+ INCREASES
4) CA2+ BINDS TO CALMODULIN
5) CA2+-CALMODULIN COMPLEX ACTIVATES MYOSIN LIGHT-CHAIN KINASE
6) MYOSIN LIGHT-CHAIN KINASE PHOSPHORYLATES MYOSIN -> ALLOWS BINDING TO ACTIN -> CONTRACTION

(DECREASE INTRACELLULAR CA2+ = RELAXATION)
What is inward current?
The flow of positive charge INTO the cell, depolarizing the membrane potential
What is found in skeletal muscle but not in smooth muscle?
Troponin
What is outward current?
The flow of positive charge OUT of the cell, hyperpolarizing the membrane potential
What is an ineffective osmole?
Urea. It is really small and has a reflection coefficient close to zero (completely permeable)
What is an action potential?
A property of excitable cells that consists of a rapid depolarization (upstroke) followed by repolarization of the membrane. Action potentials are propagating
in skeletal muscle, what occurs before depolarization of the T tubules?
depolarization of the sarcolemmal membrane
Are action potentials graded or all-or-none?
All-or-none
What is an action potential threshold?
The membrane potential at which the action potential is inevitable, and the net inward current becomes greater than the net outward current
What is the resting membrane potential of a nerve?
-70 mV, because of the high resting conductance to K
At rest, what is the state of Na channels and Na conductance in nerves?
The Na channels are closed and Na conductance is low
What happens during the upstroke of an action potential?
The membrane depolarizes to threshold
The activation gates of the Na channels open, increasing Na conductance
Because Na conductance is now higher than K's, the membrane potential is driven toward Ena
Thus, rapid depolarization during upstroke is caused by inward Na current
What is the "overshoot" of an action potential?
The brief portion at the peak of the action potential where the membrane potential becomes positive
What is the mechanism of action of tetrodotoxin (TTX) and lidocaine?
They block the voltage-sensitive Na channels of nerves, thereby abolishing action potentials
What is the sequence of events of an action potential?
Resting membrane potential
Upstroke (depolarization)
Repolarization
Refractory period
What happens during the repolarization of an action potential?
Depolarization closes the inactivation gates of the Na channel, abolishing Na conductance
Depolarization slowly opens K channels and increases K conductance to levels higher than rest
This causes the membrane potential to repolarize
Thus, repolarization is caused by outward K current
What is the "undershoot" of an action potential?
When the K conductance remains higher than at rest, even after Na channel closure. This drives the membrane potential very close to Ek
What is the absolute refractory period?
The period during which another action potential cannot be elicited, no matter how large the stimulus. This is because the inactivation gates on the Na channels are still closed
What is the relative refractory period?
The period during which an action potential can be elicited, but only if it is larger than the usual inward current. This is because the K conductance is higher than at rest, so as Em approaches Ek, it moves farther away from threshold
What is accommodation (in the context of action potential propagation)?
Occurs when a cell membrane is held at a depolarized level such that threshold is passed without firing an action potential
Occurs because depolarization closes the inactivation gates on the Na channels
Accommodation is demonstrated in hyperkalemia, where skeletal muscle is depolarized by high serum K concentrations. This closes the Na channels
How are action potentials propagated?
The spread of local currents to adjacent areas of membrane, which are then depolarized to threshold and generate action potentials
What factors increase the conduction velocity of a nerve?
Increased fiber size (increased diameter decreases internal resistance)
Myelination (myelination acts as an insulator)
How does myelin modulate nerve conduction of action potentials?
It increases conduction velocity by acting as an insulator
Myelinated nerves exhibit saltatory conduction because action potentials can only be generated at the nodes of Ranvier (gaps in the myelin sheath)
What are the general features of a chemical synapse?
An action potential in the presynaptic cell causes it to depolarize
Ca enters the presynaptic terminal and causes neurotransmitters to be released
Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane, causing a change in ion permeability and membrane potential
What effect do inhibitory neurotransmitters have upon the postsynaptic membrane potential? Excitatory?
Inhibitory -- hyperpolarize the membrane
Excitatory -- depolarize the membrane
What is the neuromuscular junction?
The synapse between the axons of motor neurons and skeletal muscle. The neurotransmitter, ACh, binds to postsynaptic nicotinic receptors
How is ACh synthesized and stored in the presynaptic terminal?
Choline acetyltransferases catalyzes the formation of ACh from CoA and choline in the presynaptic terminal
ACh is stored in synaptic vesicles with ATP and proteoglycan for later use
How does depolarization of a presynaptic membrane cause propagation of a signal through an action potential?
Depolarization opens Ca channels
Ca influx causes Ca influx, which induces exocytosis of presynaptic vesicles
How does the ACh receptor in the muscle end plate work?
The nicotinic ACh receptor is also a Na and K ion channel
Binding of ACh to the receptor causes a conformational change that increases conductance for Na and K
What is the mechanism of action of Botulinum toxin (Botox)?
Blocks the release of ACh from presynaptic terminals and completely blocks the neuromuscular action potential
What is the mechanism of action of curare?
Competes with ACh for receptors on the postsynaptic motor end plate
This decreases the size of the EPP and can produce paralysis of the respiratory muscles and death
What is the mechanism of action of neostigmine?
Inhibits acetylcholinesterase
This prolongs and enhances the action of ACh at the muscle end plate
What is the mechanism of action of hemicholinium?
Blocks reuptake of choline into the preynaptic terminal
This depletes ACh stores from the presynaptic terminal
What is the end plate potential in the postsynaptic membrane?
The contents of one synaptic vesicle (1 quantum) produce a miniature end plate potential (MEPP), the smallest possible depolarization
MEPPs summate to produce a full-fledged EPP, which is NOT an action but simply a depolarization (not to threshold) of the muscle end plate
How is the action potential of the neuromuscular junction related to muscle contraction?
Once the end plate depolarizes, local currents cause depolarization and action potentials in the adjacent muscle tissue
Action potentials in the muscle are followed by contraction
How is ACh degraded?
The EPP is transient because ACh is degraded to acetyl CoA and choline by acetylcholinesterase (AChE) on the muscle end plate
Describe the main features of myasthenia gravis
The patient makes antibodies to the ACh receptor, so there is a reduced number of AChR on the muscle end plate
This causes skeletal muscle weakness
The size of the EPP is reduced, so it is more difficult to depolarize the membrane to threshold to produce action potentials
Treatment with AChE inhibitors prolongs the action of ACh in the synapse
What is a one-to-one synapse?
A action in the presynaptic element (the motor nerve) produces an action in the postsynaptic element (the muscle)
This type of synapse is found at the neuromuscular junction
What is a many-to-one synapse?
An action in a single presynaptic cell cannot produce an action potential in the postsynaptic cell by itself
Many cells synapse on the postsynaptic cell to depolarize it to threshold
Presynaptic input may be excitatory or inhibitory
What types of inputs does the postsynaptic cell receive?
Excitatory and inhibitory. These inputs are integrated and the sum of the inputs brings the membrane potential of the postsynaptic cell to threshold, causing the firing of an action potential
What is an excitatory postsynaptic potential (EPSP)?
These are inputs that depolarize the postsynaptic cell and bring it closer to threshold
They are caused by the opening of channels that are permeable to Na and K, similar to ACh channels
They depolarize to a value about halfway between Ena and Ek
What types of neurotransmitters cause an EPSP?
ACh
Norepinephrine
Epinephrine
Dopamine
Glutamate
Serotonin
What is an inhibitory postsynaptic potential (IPSP)?
These are inputs that hyperpolarize the postsynaptic cell, moving it away from threshold
They are caused by the opening of Cl channels, so the Em approaches Ecl
What is spatial summation of synapses?
Two excitatory inputs arrive at a postsynaptic neuron at the same time, and together they produce greater depolarization
What is temporal summation of synapses?
Two excitatory inputs arrive at a postsynaptic neuron in rapid succession
Because the resulting depolarizations overlap in time, they are added in a stepwise fashion
What is facilitation (in the context of the synapse)?
Also known as augmentation and post-tetanic potentiation
This occurs after tetanic stimulation of the presynaptic neuron
Depolarization of the postsynaptic neuron is greater than expected, because greater-than-normal amounts of neurotransmitter are released due to accumulation of Ca in the presynaptic terminal
Long-term potentiation (memory) involves new protein synthesis
Describe the main features of norepinephrine
Primary neurotransmitter released from postganglionic sympathetic neurons
Synthesized in the nerve terminal and released into the synapse to bind to alpha or beta adrenergic receptors
Removed from the synapse
How is norepinephrine removed from the synapse?
Reuptake
Metabolized by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) to DOMA and NMN
What types of neurotransmitters cause an IPSP?
y-aminobutyric acid (GABA)
Glycine
Describe the main features of norepinephrine
Primary neurotransmitter released from postganglionic sympathetic neurons
Synthesized in the nerve terminal and released into the synapse to bind to alpha or beta adrenergic receptors
Removed from the synapse
How is norepinephrine removed from the synapse?
Reuptake
Metabolized by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) to DOMA, NMN, MOPEG, and VMA
What metabolite is excreted in the urine when you have a pheochromocytoma?
This tumor of the adrenal medulla secretes catecholamines, and norepinephrine degradation causes VMA to be excreted in the urine
How is epinephrine produced?
Synthesized from norepinephrine by phenyl-ethanolamine-N-methyltransferase
Secreted, along with norepinephrine, from the adrenal medulla
What is the biosynthetic pathway that produces norepinephrine and epinephrine?
Tyrosine
L-dopa
Dopamine
Norepinephrine
Epinephrine
Describe the main features of dopamine
Found in midbrain neurons
Released from the hypothalamus
Inhibits prolactin secretion (known as PIF in this case)
Metabolized by MAO and COMT
What are the actions of the receptors bound to by dopamine?
D1 receptors activate adenylate cyclase via a Gs protein
D2 receptors inhibit AC via a Gi protein
What is the molecular basis of Parkinson's Disease?
Degeneration of dopaminergic neurons that use the D2 receptors
What is the molecular basis of schizophrenia?
Increased levels of D2 receptors
Describe the main features of serotonin
Found in the brain stem
Formed from tryptophan
Converted to melatonin in the pineal gland
Describe the main features of histamine
Formed from histidine
Found in the neurons of the hypothalamus
Describe the main features of glutamate
Most prevalent excitatory neurotransmitter in the brain
Four subtypes of receptor
What are two of the important types of glutamate receptor?
Inotropic receptors (ligand-gated ion channels), including the NDMA receptor
Metabotropic receptors, which are coupled to ion channels via heterotrimeric G proteins
Describe the main features of GABA
Inhibitory neurotransmitter
Two types of receptor
What are the types of GABA receptor?
GABA A receptor -- increases Cl conductance; the site of action of benzodiazepines and barbiturates
GABA B receptor -- increases K conductance
Describe the main features of glycine
Inhibitory neurotransmitter found primarily in the spinal cord and brainstem
Increases Cl conductance
Describe the main features of nitric oxide
Short-acting inhibitory neurotransmitter in the GI tract, blood vessels, and CNS
Synthesized from arginine by NO synthase in the presynaptic nerve terminals
Permeant gas that diffuses to target cells
Also acts to activate guanylyl cyclase in a variety of tissues, including vascular smooth muscle
What is the general structure of a muscle fiber?
Each fiber is multinucleated and acts as a single unit
Contains bundles of myofibrils
Surrounded by sarcoplasmic reticulum
Invaginated by T tubules
Each myofibril has interdigitating thick and thin filaments arranged longitudinally into sarcomeres
What defines a sarcomere?
You count Z line to Z line
What gives skeletal muscle its unique banding pattern?
The presence of sarcomeres
What is the structure of a muscle thick filament?
Made of myosin
Thick filaments are found in the B band at the center of the sarcomere
Each myosin has two heads attached to a single tail. The heads bind ATP and actin, and are involved in cross-bridge formation
What is the structure of myosin?
Six polypeptide chains -- one pair of heavy chains and two pairs of light chains
What is the structure of muscle thin filaments?
Present in the I bands and anchored at the Z lines
Interdigitate with the A band
Contain actin, tropomyosin, and troponin
How does the troponin complex regulate muscle contraction?
Troponin is a regulatory protein that permits cross-bridge formation when it binds to Ca
Troponin T attaches the troponin complex to tropomyosin
Troponin I inhibits the action of actin and myosin
Troponin C binds Ca and permits the interaction of actin and myosin
What are T tubules?
They are an extensive tubular network open to the extracellular space that carry depolarization from the sarcolemma to the cell interior. They are found at the junction of A and I bands, and contain a voltage-sensitive dehydropyridine receptor that undergoes a conformational change upon depolarization
What is the sarcoplasmic reticulum?
Internal tubular structure that stores and releases Ca for excitation-contraction coupling
Terminal cisternae make contact with the T tubules in a triad
Membrane has a Ca-ATPase that transports Ca into the SR
Contains Ca loosely bound to calsequestrine
Releases Ca into the cell interior through the ryanodine receptor
What are the steps of excitation-contraction coupling?
Action potentials in the muscle cell membrane depolarize the T tubules
The dehydropyridine receptors in the T tubules undergo a conformational change
This opens Ca release channels (ryanodine receptors) in the SR
Ca is released into the cytoplasm from the SR lumen
Intracellular Ca increases and binds to troponin C, initiating the cross-bridge cycle so that the muscle contracts
Ca goes back into the SR through the Ca ATPase and the cross-bridge cycle stops (muscle relaxes)
What are the steps of the cross-bridge cycle?
Ca binds to myosin and the cross-bridge cycle begins:
When myosin is not bound to ATP, it is tightly attached to actin
ATP binds myosin and causes a conformational change such that myosin releases actin
Myosin is displaced toward the plus end of actin. This involves ATP hydrolysis -- ADP remains attached and P dissociates
Myosin attaches to a new site on actin; this is the power stroke
ADP is released and myosin returns to its original rigor state
As long as Ca is bound to troponin C, this cycle repeats
What is the mechanism of muscle relaxation?
Ca is reaccumulated by the SR Ca-ATPase (SERCA)
Intracellular Ca concentration decreases and Ca is released from troponin C
Tropomyosin again blocks the myosin-binding site on actin
What is the mechanism of tetanus?
If a muscle is stimulated repeatedly, more Ca is released from the SR
This causes a cumulative increase in intracellular Ca, extending the time for cross-bridge cycling
The muscle does not relax during this time
What are isometric muscle contractions?
Contractions at a fixed length. The length (preload) is fixed, the muscle is stimulated to contract, and the developed tension is measured. There is no muscle shortening.
What are isotonic muscle contractions?
The load against which the muscle contracts (afterload) is fixed, the muscle is stimulated to contract, and shortening of the muscle is measured.
What is the length-tension relationship of muscle?
Measures tension during isometric contractions when the muscle is set to fixed lengths (preloads)
What is passive muscle tension?
The tension developed by stretching the muscle to different lengths
What is total muscle tension?
The tension developed when the muscle is stimulated to contract at different lengths
What is active muscle tension?
The difference between total and passive tension, representing the active force developed from muscle contraction
Active tension is proportional to the number of cross-bridges formed
How does the degree of muscle stretch affect active tension?
Tension is maximal when there is maximum overlap of thick and thin filaments
When the muscle is greatly stretched, there is less overlap
When the muscle length is decreased, the thin filaments collide and can't generate a good power stroke, so tension is decreased there too
What is the force-velocity relationship of muscle?
Measures the velocity of shortening of isotonic contractions when the muscle is challenged with different afterloads
The velocity of shortening decreases as the afterload increases
How does smooth muscle differ from skeletal muscle?
Thick and thin filaments are not arranged in sarcomeres, so it does not appear striated. Contraction is involuntary. Also, there is no troponin
What are the main features of multi-unit smooth muscle?
Found in the iris, ciliary muscle of the lens, and vas deferens
Behaves as separate motor units
Little or no electrical coupling between cells
Densely innervated; contraction is controlled by neural innervation
What are the main features of urinary smooth muscle?
Most common type of smooth muscle, found in the uterus, GI tract, ureter, and bladder
Spontaneously active (exhibits slow waves) and has pacemaker activity
Pacemaking is modulated by hormones and neurotransmitters
Lots of electrical coupling between cells to allow for coordinated contraction
What are the steps of excitation-contraction coupling in SMOOTH muscle?
Depolarization of the cell membrane opens voltage-gated Ca channels
Ca enters the cell
This causes additional release of Ca from the SR
Hormones and NTs can also cause SR Ca release through IP3-gated Ca channels
Intracellular Ca concentration increases
Ca binds to calmodulin, and the Ca-calmodulin complex binds to/activates myosin light-chain kinase
MLCK phosphorylates myosin and allows it to bind to actin
Contraction occurs
What ion mediates the upstroke of the action potential in smooth and cardiac muscle?
Ca
What types of muscle exhibit a plateau in their action potential?
Atria, ventricles, and purkinje fibers in the cardiac muscle
What type of muscle has the shortest action potential duration? What about the longest duration?
Shortest -- skeletal
Longest -- cardiac
What types of muscle use Ca-troponin C for contraction?
Skeletal and cardiac muscle