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133 Cards in this Set

  • Front
  • Back
Temporal Summation
A single input potential with a long duration but small amplitude, may not reach threshold on it's own..the sum of all the small potentials it creates collect in the soma of the neuron and add up to reach threshold and cause an AP.

(IPSP's and EPSP's can summate as well...competing against each other to determine cell charge.)
Spatial Summation
Several axon terminals come together and meet at ONE postsynaptic cell. Many to one input, output distribution. The sum of all of their stimulii/ NT's reaches threshold and causes and AP
Neurotransmitters are inactivated by:
1) Enzymatic Degradation in the synapse
2) Reuptake into terminals (of presynaptic cell and into nearby astrocytes)
3) Diffusion
4) A combination of these
Classes of primary neurotransmitters
1) Acetylcholine
2) Amines
3) Amino Acids
4) Peptides
Peptide neurotransmitter classes
Opioid Peptides
Hypothalamic Releasing Hormones
Pituitary Peptides
Gut-brain peptides
Dale's Principle
Since there does not appear to be a mechanism permitting differential secretion, it is a reasonable working hypothesis that ALL TERMINALS OF A NEURON SECRETE THE SAME THING. (Dale thought that only one NT for each neuron.) (He was wrong).

There are often two diff types of NT at one nerve terminal (Co-localization.) However, all terminals of the same neuron have only this pair.
Excitatory Post Synaptic Potentials
Depolarize the post synaptic terminal.
Involve increases in Na+ and K+ conductance
Inhibitory Post Synaptic Potientials
Hyperpolarize the post synaptic terminal
Involve increases in K+ and/ or Cl- conductance.
--> The K hyperpolarizes the cell. (decreases cell voltage)
--> The Cl stabilizes or clamps membrane voltage which makes excitatory depolarizations less effective at reaching threshold.
Compare the duration of post synaptic potentials with the duration of action potentials
AP's: Ionic channel opening and closing is very FAST and amplitude is HIGH.

Post-synaptic potientials: Have passive electrical properties that delay repolarization, so the post synaptic membrane stays depolarized longer....creating a LONGER duration. (this allows for temp. and spat. summation)
Describe a ligand gated ion channel and give an example:
5/4 structure (except for the glutamate receptor - 4/3)
Neurotransmitter binds to protein. This binding causes it to open it's ion channel and allow the influx of a specific ion.

Ex: ACh and it's ligand-gated channel at the NM junction
Explain second messenger system
Instead of a direct system where a NT binds to a receptor and the protein opens an ion channel....there is a second messenger system interposed b/n ligand recognition and the alteration of ion channel conductance.

Can also influence NT synthesis/ degradation, receptor sensitivity and #, and other modifications of existing intracellular protein function.
Adenylate cyclase- Cyclic AMP System
Second messenger System: One example is: Beta Adrenergic Receptors (NT is epinephrine or norepinephrine)

-->NT binds to receptor on the post synaptic membrane.
-->Receptor binding causes a coupling G protein to activate Adenylate cyclase (the effector protein).
--> Adenylate cyclase synthesizes cyclic AMP (the second messenger)
-->Cyclic AMP acts inside the cell to activate Protein kinase A.
-->Protein kinase A phosphorylates various proteins to change their activity (change the movement of ions.)

(all of these steps can be targeted by drugs or altered by the body (plasticity) cAMP is later degrated by an enzyme
Calcium-calmodulin System
Second Messenger System
--> Produces an activated complex which can mediate a variety of intracellular actions
Phospholipid System
Second Messenger System: Glutamate is the NT. MGluR - receptor.
-->Binding causes G-protein to activate phospholipase C (effector protein)
--> Phos.-C generates 2 intracellular signals (second messengers):
---->Diacylglycerol (DG): increases Protein Kinase C.
----> Inositol triphosphate (IP3) - binds to calcium receptors and causes Ca ion release from intracellular storage depots. this can influence Ca binding proteins to open ion channels.
--> Protein Kinase C increases protein phosphorylation, which will open ion channels.
Neuron Doctrine
The nervous system is not composed of a connected network but many discreet individ. signaling elements (neurons). There are 10^12 neurons in the brain. They share basically the same function and design. However, they are organized into functional systems that are very specific. They communicate via synapses.
Dynamic Polarization
The direction of the polarization is unilateral and goes in one direction.
Connectional Specificity
Each connection of neuron to neuron to target organ, etc is specific to the task at hand. All the connections are specific and correctly organized.
The functional organization of neurons is described by:
Reflex arcs

(a negative feedback control loop)
Where do Action potentials originate?
Axon Hillock - an integrative trigger zone
2 types of input zones
Receptor: Stimulii from outside the body trigger receptors which initiate an input potential at the sensory neuron. (usually metotrophic)

Synaptic: NT's bind to receptors of ligand gated ion channels and cause them to open or close.
Graded electrical potentials
- produced by input zones - the amplitude and duration depends on the size of the stimulus or on the concentration of NT's in the synapse. (hence they are graded)
Resting membrane potential results from:
1) Ionic concentration gradients
2) Selective ionic permeabilities of membrane proteins
3) ATP-ase pump (adds -4mV to the MP)
...hence RMP is a steady state requiring energy.
Nernst Equation
E= -60 x log10 [Inside]/ [Outside]

The intracellular voltage that will balance the concentration gradient of a ion across the cell so that there is no net movement of ions across the cell. = Equilibrium Potential
Characteristics of the ATPase pump
1) Saturable and carrier mediated
2)Temp dependent consistent w/ enzyme kinetics
3)Substrate dependent for rxn velocity (Pump rte is proportional to ion leakage)
4) Requires ATP
5) Specifically inhibited by cardiac glycoside drugs (digoxin).
Where does summation of potentials occur?
sensory receptors, synaptic inputs on dendrites and soma.
Sodium Ion Channel Characteristics
Voltage gated.
Fast duration.
Large Amplitude. (6000x inc in 1 msec)
Depolarizing.
Have three positions: Activated, Inactivated, Closed
Sodium ions flow IN. NOT out.
Sodium ion selectivity due to interactions with pore wall that dehydrate sodium ion as it passes filter. Potassium does not interact so remains hydrated and too big for the sodium channel.

Inactivation gates blocked by pronase.
Gate opening blocked by Tetrodotoxin and Saxitoxin and Local Anesthetics.
Characteristics of voltage gated. K+ ion channels
Repolarize.
1000x K efflux in 3 msec.
Unidirectioal: K+ flows OUT, not in.
Open and close slowly.
K+ Selective: large enough to allow hydrated K ion thru but small enough to keep hydrated Na ions out.

Blocked by tetraethylammonium
What are the passive electrical properties of a neuron?
Input potentials and the parts of AP's that do not require ATP.
1) Temporal Summation & time constant
2)Spatial Summation & Length/Space constant
3)Conduction Velocity and diameter/ myelin
Explain how the time constant affects temporal summation
The longer the duration (tao/ time constant) of an input potential, the better the chance that inputs will summate and maybe even reach threshold.

(If the duration (tao) is too brief for the input potentials to summate, if you increase the frequency of the input potentials, then they can summate and maybe reach threshold.)
Explain how the space/length constant (lambda) effects spatial summation.
The length/space constant (lambda) = the distance along the input region that an input potential's voltage has decayed by 63%.

The longer the lambda, the better the chance that potentials will summate and maybe reach an AP.

Also, inputs that occur closer to the axon hillock are more influential at determining summation/ threshold because they have a shorter distance to travel.

Increase lambda, increase speed of depolarization.
Explain how axon diameter and myelin affect the conduction velocity and membrane resistance.
The larger the axon diameter, the faster the conduction velocity. Larger axon diameters allow for decreased resistance down the axon as well.

Myelin insulates the axon. It increases membrane resistance and increases capacitance (charge) across the membrane. This speeds up conduction velocity 100x.
Capacitance
the ability of the cell membrane to hold an electrical charge. (Depends on the membrane thickness and the solubility of membranes.)

(Capacitance across a membrane doesn't change with an AP. It's not the charge itself, it's the ability to hold the charge. It endows the properties that allow an AP.)
Resistance
Opposition to the passage of current
What component of a cell/ axon is the main determinant of the ability to have an AP?
The integral proteins in the cell membranes, specifically in the axon. They open and close to permit the movement on ions that conducts the signal via depolarization.
Threshold Potential
The amount of depolarization necessary to trigger an action potential at the axon hillock. (NOT constant. Will vary as a function of the state of the NA/ K ion channels...open, inactivated, or closed. EX: threshold increases during AP refractory periods.)
Depolarization to reach threshold varies as a function of:
Initial NA/K ion state.
What is the difference in membrane response from hyperpolarization and depolarization of the membrane?
When it is depolarized sufficiently, you see an active membrane response that can burst into an action potiential. Hyperpolarization does not do this.
What did Hodgkins and Huxley discover?
Studied a squid axon in extracellular bath. Put a voltage clamp on it to study changes in M.P.
- AP's all depend on the independent voltage gated ion channels (proteins.)
-Conduction is a reciprocal of resistance.
What structural component of ion channels allows them to open and close?
The 4th trans-membrane span of the protein is a VOLTAGE SENSOR. It rotates when positively charged. This causes a conformational change of the pore loop to open or close the channel.
Describe the structure of the voltage-gated ion channels (common characteristics):
All VG proteins are made up of 4 units. Each unit has 6 transmembrane spans. The units circle up and the inside is an aqueous pore. (Where the ions go through.)
Describe the mechanics of how a sodium channel inactivates.
Inactivation is like a ball and chain. It only inactivates on the intracellular side, between units 3 and 4. (It takes a certain amt of time after activation for the inactivation to occur...like a slowly shutting screen door.)
What drug blocks the ability of Na ion channel to inactivate?
Pronase (an enzyme.)

It PROLONGS the AP duration but depolarization and repolarization still occur.
What are some diff types of potassium channels?
1) Voltage Gated
2)Calcium Activated
3) 2- Pore type (leakage)
What neurotoxin blocks the inward flux of sodium ions?
Tetrodotoxin and Saxitoxin

Tetrodotoxin - from blowfish. NO AP. Tingling to paralysis. Sodium channel cannot open.

Saxitoxin - from red algae - causes Paralytic Shell Fish Poisoning. NO AP.
What neurotoxin blocks the outward flux of potassium?

How does this affect an AP?
Tetraethylammonium
-Blocks the potassium channels from opening.
-Repolarization STILL OCCURS
-There is a slower repolarization associated with the passive electrical properties and sodium potassium pump.
What ion channel do Local Anesthetics block? Are they reversible?
Sodium channels just like tetrodotoxin causin paralysis.
(Lidocaine)

Reversible - wear off with time.
What happens to AP when you combine pronase and tetraethylammonium?
Pronase blocks the sodium inactivation gate. (sodium channels stay open.)

Tetraethylammonium blocks the K channels (can't open.)

-->Na channels open and you have your LAST ACTION POTENTIAL...THEN PARALYSIS.
What did the patch clamp experiment do?
Permitted the measurement of a single ion channel conductance.

Found that individually they all function a little differently but their average function is reflective of the theoretical model.
Recovery of sodium ion channel from inactivation requires ______ and _______.
Repolarization
and
Time.

**must be a long enough time interval for channels to close. This is the absolute refractory period.
Absolute Refractory Period
After depolarization, sodium channels are either open or inactivated but not closed.

No action potential is possible.
Threshold - INFINITY
Relative refractory period
Immediately follow Absolute Refractory Period

Not all of the Na channels are closed but SOME are...so they can be activated.
K channels are open with K influx. This RAISES THE THRESHOLD.

CAN STILL HAVE AN AP BUT THERE IS A HIGH THRESHOLD THAT DECREASES WITH TIME.
-Length of relative refractory period is until you reach RMP.
___________________ explains why sustained sensory stimulii of varying amplitudes result in different frequencies of action potential.
The progressively decreasing threshold during relative refractory period.

(If the depolarization of the stimulus is large, it can catch the relative refractory period threshold at an earlier point, thereby increasing the frequency of the AP.) It can't refire fast if it can't overcome rel. ref. high thresholds.)
Propogation of AP's along myelinated axons, jumping from one Node of Ranvier to another.
Saltatory conduction

(Ion channels are localized at these nodes so that the AP is rejuvenated.)
Nodes of Ranvier
Unmyelinated gaps of the axon where the ion channels are located. AP is rejuvenated.
A condition of demyelination that slows or blocks the conduction of AP's
Multiple Sclerosis
Myathenia Gravis
Explain what happens with hyperkalemic periodic paralysis or channelopathy (A genetic disorder of horses)
Faulty inactivation of mutant sodium channels of skeletal muscle.

--Increased duration of AP's
--Increased duration of open K ion channels
--Increased efflux of K ions
--Hyperkalemia - increased freq of AP's and hypertrophy.
--Eventually unable to have an AP due to increased [K].
--PARALYSIS
What causes the exocytosis of neurotransmitter vesicles into the synapse?
The opening of a Ca ion channel.

Ca rushes into the end terminal and binds with synaptotagmin in the SNARE complex, which causes membrane fusion and exocytosis.
Neuromuscular Junction AP transmission.
Where a post-synaptic cell meets a skeletal muscle cell.
-AP travels down axon and gets to axon terminal. Depolarization there triggers the opening of calcium ion channels.
--Ca binds to synaptotagmin, which triggers the exocytosis of NT vesicles by SNARE, releasing ACh into synapse.
--ACh diffuses across synapse to bind at ligand gated nicotinic receptors, stimulating the opening of Na/K ion channels.
--Na and K both move thru ion channel. Their driving force varies respective to their equilibrium potentials (Na flow influx is higher).
--Na Influx is so large that depoloarization is SUPRATHRESHOLD. There is no need for temperal or spatial summation at the NM Junction.
--Depolarization of skeletal muscle cell causes sarcoplasmic
reticulum to release calcium via calcium ion channels.
--The released calcium causes muscle to contract.
--The enzyme cholinesterase eventually degrades the ACh left in the synapse and the pieces are taken back up by the presynaptic terminal.
What are some characteristics of neuro-muscular junction design?
One-to-one excitation of muscle by virtue of large amplitude end-plate potential.
Anatomic specialization closely apposes pre-and post-synaptic elements.
Ca2+ channels, vesicles clustered around active release zones with receptors directly across cleft.
End plate potential
The depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction

EPP is a graded local potential: (size related to amount of acetylcholine), decrements as it spreads (compare to all or none action potential conducted without decrement)

EPP normally is SUPRATHRESHOLD so that it triggers one muscle AP for every motorneuron AP
What ligand gated ion channel receptor is at the neuromuscular junction? What NT?
ACh to a nicotinic receptor.
What drug blocks nicotinic receptors?
curare
causes paralysis
What drug blocks muscarinic receptors?
Atropine
Two types of Cholinergic receptors
Nicotinic
-->work by opening an ion channel (ligand gated)
-->Ionotropic Receptors
-->At neuromuscular junction and preganglionic synapses in ANS.

Muscarinic: M1 and M2

-->Metabrotrophic Receptors: G-Protein second messenger systems: M1 (IP2/DAG). M2 (decreases cAMP)
Superfamilies of Integral Proteins
Voltage gated Ion channels
Ligand gated Ion Channels
Metabotrophic Ion Receptors
Characteristic structure of ligand gated Ion Channels
Five units, each with four membrane spans.
(Except for glutamate's ligand receptor protein, which is 4/3).
Ligand gated Ion Channel NT's
Glycine (IPSP) (Cl- selective) (5/4)
GABA-a (IPSP) - Cl- selectice (5/4)
ACh (nicotinic) (cation selective) (5/4)
Glutamate - (EPSP) (Ca, Na, K cation selective) (4/3)
Serotonin (5-HTm receptor) (cation selective) (5/4)

(some of these can act at other types of receptors as well.)
What ligand gated ion channel is an exception to the 5/4 norm of protein structure?
The one that binds with Glutamate. It's 4 units with 3 transmembrane spans.
GABAa Receptor Properties
Ligand Gated
Chloride Ion Selective
IPSP (hyperpolarizes and inhibits)
Depressant drugs can bind NOT at but NEAR the GABA receptor and potentiate the IPSP effects: Benzos, barbs, propofol, alcohol, some neuro-steroids.

(GABA NT must bind as well for them to work....they potentiate it but can't work without the NT.) They do not bind at the GABA receptor itself but elsewhere on the molecule and the binding sites are all diff/ specific for each drug.
NMDA Receptors: What NT? Selective for what ions? What structures? What else?
Receptors for Glutamate.
4/3 structure (exception)
Selective for Ca, Na and K+ ions,
But have a high permeability for Ca ions.
EPSP caused by Ca influx.
It's ion channel is occluded by a Mg ion, EVEN when it is opened by Glutamate.
A depolarization from other inputs in the vicinity is necessary to move the Mg ion.
(This characteristics allows for some synaptic plasticity.)
G Protein Receptor Structure
Serpentine Integral Protein
Only ONE unit with 7 transmembrane spans that loop together making pore that is the NT binding site.
Intracellular tail is the G-protein binding site.
G Protein Coupled, Second Messenger Mediated Processs
-NT(the first messenger) binds to receptor and activates G-Protein inside the cell.
-G Protein dissociates into subunits.
-Some of these subunits go to an effector protein in the cell membrane and activate it to make an intracellular signal (the second messenger).
-The second messenger influences the opening of an ion channel .

Examples:
Sensory receptors (odorant molecules, photons)
Chemical receptors (NT's)
Ways Ca can get into cell from outside
Voltage gated Ca channel
Ligand gated Ca channel
Whera is Ca released from organelles inside the cell?
IP3 receptor ion channel on membrane of the Endoplasmic Reticulum

RYANODINE receptor on membrane of Sarcoplasmic Reticulum in muscle cells
Beta Adrenergic receptors are associated with increased______
Cyclic AMP.
Adrenergic Recepters use _______________ type protein receptors...
G-Protein coupled second messenger system
Muscarinic Cholinergic receptors use __________type protein receptors.
G-Protein coupled second messenger system
Peptides all use ___________ protein receptors.
G-Protein coupled second messenger system
A neurotransmitter receptor gene disorder (autosominal dominated) characterized by exaggerated startle response.
Hypereplexia
Familial Startle Disease

Glycine is a major inhibitory transmitter in the spinal cord. Sub-convulsive doses of the receptor antagonist STRYCHNINE induce hypertonia and exaggerated startle.
Peptide NT's are synthesized where?
In the cell body because they are peptides and require Endoplasmic Reticulum.
Beta Adrenergic receptors work by increasing....?
cAMP
What are SNARE's?

What are they made of?
SNARE's are receptables that Dock NT vesicles and FUSE them to the cell membrane.

They are composed of:
NSF Proteins -n ethyl-malemide sensitive fusion protein

SNAP - soluble NSF attachment protein

They also participate in trafficking the vesicles in the ER-golgi apparatus. (ie func is not specific to the NT vesicles).
Name proteins involved in synaptic vesicle processing, docking, and fusing:
Synaptobrevin (VAMP)- vesicle associated membrane protein.
Syntaxin- on cell membrane
Synaptotagmin - has Ca binding sites. On vesicle membrane
SNAP - on cell membrane
Which Vesicle associated membrane protein is triggered by the influx of calcium? ie has a Ca binding site)
Synaptotagmin
Name two vesicle membrane proteins:
Synaptobrevin
Synaptotagmin
Explain the structure of the calcium ion channel protein
4 units, each with 6 transmembrane spans.
The 4th span is the voltage sensor.

(Just like ALL VG ion channel proteins.)
Explain the Docking and Fusion process of synaptic vesicles
Vesicle's membrane proteins(synaptobrevin and synaptotagmin) and SNAP/ Synaptotaxin proteins on cell membrane entwine together to form a SNARE complex. This holds the vesicle close to the presynaptic cell membrane.

An AP leads to the opening of voltage gated Ca channels. Ca influx. Ca binds to synaptotagmin.

This triggers the Fusion of the vesicle with the membrane. NT is dumped into the synapse.

Left over vesicle membrane is taken back up by the terminal.
What toxin enzymatically cleaves SNARE docking proteins preventing NT release into the synapse
AND
is selective for Cholinergic Neurons?
Clostridium botulium

- Prevents the release of ACh into the synapse. For motor neurons, there is not ACh release at the NM junction---> Flaccid Paralysis occurs.
Boutulism from old canned goods causes this. Botox injections cause this (paralyze the facial muscles.) Also used for eye muscle disorders. Cervical dystonia
Paralysis lasts 3 months.
What toxin enzymatically cleaves SNARE docking proteins preventing NT release into the synapse
AND
is selective for inhibitory interneurons?
Clostridium tetanus (TeTX)

Skeletal muscles are unable to relax via inhibitory signals. Causes hyperexcitation of muscle and tetanic contraction. Can't breathe or move.
What toxin works by blocking the post-synaptic receptors? What happens?
Curare AND snake venom alpha toxins.

They cause paralysis.
What poison inhibits the action of acetylcholinesterase?

What happens?
Nerve Gas

Hyper-excitability of muscles due to increased ACh levels.
What toxin ACTIVATES sodium channels and thereby disrupts action potentials?
Batrachotoxin (a neurotoxin from Poison dart frogs.)

(not sure if I need to know this one for the test.)
How are peptide NT's removed from synaptic cleft?
They diffuse away.

(Makes their duration of action significantly longer.)
How are small sized NT's removed from synaptic cleft
Reuptake by presynaptic terminal & nearby astrocytes.

(ACh is degraded first by acetylcholinesterase and then reuptake occurs of the pieces.)
What are some NT reuptake inhibitors and how do they work?
Cocaine - inhibits the reuptake of dopamine and NE. Excess dopamine and NE in the synapse causes an increased SNS response.

Serotonin reuptake inhibitors: antidepressants. Increase serotonin in synapse, elevate mood.
Electrical Synapses
On Gap Junction Proteins on cell membranes. The proteins connect membrane to membrane and form a connection.

Ion movement via this electrical connection is faster than chemical synapses.
Why does the body choose chemical synapses over Electrical synapses??

...electrical synapses are faster!!
Elec synapses are not unidirectional like chem. synapses so it could mess up the flow of signal.

Chemical synapses allow for temporal and spatial summation of inputs, while elec does not.

Chemical synapses are able to display PLASTICITY, meaning they can adapt to needs by changing the design or quantity of ion channels, receptors, etc, while electrical cannot. (plasticity is the basis or learning and memory.)

So chemical is more valuable.
Axonal Transport
Neural filaments in cytoskeletal architecture along which elements can be moved from cell body to terminal and vice versa.
What did Otto Loewi Do?
Stimulated the vagal nerve in a turtle. Discovered that the ACh receptor in the fluid around the heart cells carried the ability to send a signal. (slow down the heart)
Criteria that define a Neurotransmitter
1) It's present w/n the neuron
2) It has to be released by Ca-dependent depolarization
3) It has to have specific receptors for that NT on the postsynaptic cell.
Small Molecule Neurotransmitters
ACh

Amino Acid NT's
--> Glutamate
--> GABA

Biogenic Amine NT's:
Histamine
Serotonin (5HT)
Catecholamines:
-->Dopamine
--> Norepinephrine
-->Epinephrine

**These leave synapse via reuptake.
**Are released with low frequency AP's
**Are stored in clear core small vesicles.
Glutamate
Amino acid neurotransmitter.(small molecule)
Fast-acting
Excitatory
Metabotrophic
It's ligand gated receptor proteins is 4/3 structure
GABA
Amino acid neurotransmitter. (small molecule)
Fast-acting
Inhibitory
Binds to GABAa receptors opening a Cl ion channel.
Peptide NT's
Amino acids connected by peptide bonds.
-->Hypothalamic releasing factor NT's (somatostatin)
-->Opiod Peptides (endorphin)
-->Pituitary Peptides (vasopressin)
-->Gut-Brain Peptides
-->Angoiotensin
Where are small molecule NT's synthesized?
In the axon terminal. (enzymes travel down axon from the cell body)
Where are peptide NT's synthesized?
In the cell body.Pre-peptides are then moved via axonal transport to the terminal. where they are modified and stored.
Colocalization
At most nerve terminals, there are two diff NT's...usually one small molecule NT and one peptide NT.
Differential Release of Co-localized Transmitters
At most nerve terminals, there are two diff NT's...usually one small molecule NT and one peptide NT.

The small molecule NT is packaged in smaller, clear core vesicles (closer to the terminal membrane).

The peptide NT is packaged in larger, dense-core vesicles

At low frequency stimulation, there is only localized [Ca] increase closer to the terminal membrane...where the small molecule NT vesicles rest. So only they are released.

At high frequency stimulations, there is a more diffuse increase in [Ca], and both types are released...small first.
EPSP
Excitatory Post Synapsic Potential

NT Depolarizes postsynaptic cell.

Ex: Glutamate
IPSP
Inhibitory Post Synaptic Potential.

NT Hyperpolarizes postsynaptic cell.

Ex: GABA
How do inhibitory NT's work?
1) Receptor protein opens a K+ ion channel allowing K+ to leave the cell.
OR
2) Receptor protein opens a Cl- channels allowing Cl- to flow into cell (Ex: GABAa)

...making cell more negative.
_________ of postsynaptic potentials is the basis of integrative processing in the nervous system.
Summation

(EPSP and IPSP's summate).
Two types of nicotinic receptors
Neuronal (at the preganglionic synapse. )

Muscular (at the neuromuscular junction.)
Two types of muscarinic receptors
M1 - (IP3/DAG)

M2 - (decreases cAMP)
Nicotinic receptors are blocked by
Curare
Muscarinic receptors are blocked by
Atropine
Ligand gated ion channel anatomy/ structure
FIVE units, each with FOUR membrane spans.

Circle up and form a pore for ions to go thru.

One Exception: The glutamate ligand gated channel has 4 units with 3 transmembrane spans.
NT's that can act at ligand gated ion channels
Glutamate - receptor is cation selective (4/3 design), mainly Ca inflow, and blocked by Mg. Excitatory and fast.
GABA - GABAa Receptor is Cl- selective. Inhibitory and slow.
ACh - nicotinic receptor is cation selective
Serotonin - (H-25) receptor is cation selective
Name some drugs that influence GABAa function. How to they bind to GABAa?
Benzodiazepines (valium), barbituates, propofol, alcohol, and some neuro-steroids.

They bind to sites near the GABA binding site and increase the potency of GABA transmission. (GABA has to bind too.)
How are photons of light and odors transmitted to the sensory neuron?
Odor and LIght receptors...which use G Protein second messenger systems to cause ion flux.

G proteins are ubiquitous tranducers (couple things) for a wide variety of physiological relevant signals.
Explain how Dopamine triggers a G Protein Second Messenger System with a D2 receptor and what happens
-->Dopamine binds to a Dopamine D2 receptor
--> This activates an inhibitory G Protein to decrease the amt of Adenylyl Cyclase (the effector protein)
--> This leads to less production of CAMP (the second messenger)
-->This leads to less Protein Kinase A
-->This leads to Decreased Protein Phosphorylation

(Therefore, dopamine causes a reversed second messenger system of Epinephrine and NE. )
Does dopamine increase or decrease CAMP?
Both.
D1 receptors - Increase cAMP
D2 receptors - Decrease cAMP
What are the second messengers for the Phospholipase C second messenger system?
Diacylglyceral - Activates Protein Kinase C to increase protein phosphorylation.

and

Inositol triphosphate (IP3) - binds to calcium receptors and causes Ca ion release from intracellular storage depots. this can influence Ca binding proteins to open ion channels.
What is the second messenger for the Adenylate Cyclase effector protein?
Cyclic AMP

It activates Protein kinase A.
-->Protein kinase A phosphorylates various proteins to change their activity (change the movement of ions.)
--> It also can phosphorylate CREB to cause alter protein transcription
--> It can also phosphorylate Tyrosine hydroxylase to alter the synthesis of catecholamines (E and NE).
What enzyme metabolizes cAMP
cAMP Phosphodiesterase
How does the cell get rid of Calcium?
-->Ca/Na+ Exchange pump (antiport - secondary active transport.) Ex in heart.
-->Active Ca/H+ Pumps
-->Ca-binding buffer proteins (get it out of circulation)
-->Active Ca pumps on membranes of organelles that pump Ca back into storage.
How does calcium produce an effect in the cell?
Binds to calcium receptor proteins
-->Synaptotagmin
-->Calmodulin
How do protein kinases work?
They add phosphate groups to targets when activated. The phosphorylation opens an ion channel.
How are open ion channels phosphorylated by protein kinases later reclosed?
Protein phosphatases dephosphorylate them and cause them to close.
What can protein phosphorylation by protein kinase do other than open protein ion channels?
Can influence other types of proteins to alter their actions.
Example:
-->Synthesis of catecholamine NT's: Tyrosine hydroxylase is the rate limiting enzyme in catecholamine synthesis. (changes L-tyrosine into Dihydroxyphenylalanine (DOPA).
-->When protein kinases phosphorylate tyrosine hydroxylate, they can regulate the enzymes activity...either increasing or decreasing it, adn thereby alter the release of catecholamines.

PK can ALSO affect genetic transcription by phosphorylating CREB
Explain CREB
cAMP Response Element Binding Protein.

When adynylate cyclase activates cAMP which activates PK-A, PK-A phosphorylates stuff, including CREB.
-->There is a cAMP "response element" (CRE) on the DNA that can bind with phosphorylated CREB
--> this influences transcription to alter protein synthesis.
Adrenergic Receptors
Alpha 1&2 (decrease cAMP)
Beta 1&2 (increase cAMP)
Do all peptide NT's bind with metatrophic receptors or ionotrophic receptors?
Metatrophic receptors.