Synaptic Unit 3

I actually cannot with this class

omega profiles

round shapes found in the presynaptic nerve terminal after axon stimulation, indicating vesicular release

pit

hole in the presynaptic membrane where protein was split from

capacitor

structure that can separate charged particles but also accumulates charge; larger membranes store more charge

amperometry

use a carbon fiber and measure the redox reactions that bump into it; for example, norepinephrine oxidizes when it lands on the carbon fiber, so can measure neurotransmitter release which coordinates to capacitance

synaptotagmin

calcium sensing vesicle-bound protein with two calcium binding sites; binds to CORE complex to prime vesicle for release

syntaxin

SNARE protein that forms CORE complex; in folded form before docking, which means high affinity for SynPrInt site

SNAP-25

SNARE protein that forms CORE complex

VAMP/synaptobrevin

SNARE protein that forms CORE complex; associated with vesicle prior to docking

chaperone proteins

proteins that bring synaptic vesicles to the active zone

Munc-18

protein that keeps syntaxin in a folded configuration until the vesicle is ready to dock

SynPrInt site

site on Ca2+ channel which binds to folded syntaxin and other CORE proteins, which allows Ca2+ channels to be closely associated with docked vesicles

SynPrInt peptide

protein that binds to the SynPrInt site instead of syntaxin, therefore preventing syntaxin from binding to voltage-gated Ca2+ channels and reducing release and abolishing synchronous vesicle release

C2A

calcium binding site of synaptotagmin closer to the vesicle

C2B

calcium binding site of synaptotagmin of which the affinity directly corresponds to how much neurotransmitter is released

synaptotagmin 1

most common form of synaptotagmin; responsible for coordination between calcium influx and transmitter release

short term synaptic plasticity

ability of synapse to change moment to moment

synaptic strength

probability that presynaptic neuron releases transmitter and how much of a postsynaptic response you're going to get

paired-pulse facilitation

second EPSP greater than first due to residual bound calcium left over from weak synapse and weak vesicle depletion

paired-pulse depression

second EPSP smaller than first due to strong vesicle depletion and not much residual bound calcium left over

tetanic potentiation

EPSP does not continuously go up because there is a decrease in the amount of vesicles; balance of residual bound calcium and vesicle depletion contributes to EPSP size

buffer saturation hypothesis

some calcium is bound by calcium buffer proteins, which become saturated so that the next round of calcium can more freely interact with synaptotagmin

calcium channel modulation hypothesis

calmodulin receives some calcium, which increases conductance of calcium channel and therefore calcium current when next round of calcium comes through; more common in P/Q channels but less often in general than calcium buffers

synaptotagmin 7 hypothesis

some calcium binds to syt-7, which holds it and interacts with syt-1 so that there can be more syt-1 NT release (increased affinity)

synaptotagmin 7

less common form of synaptotagmin tethered to the plasma membrane, not the vesicle membrane

habituation

reduction in responsiveness to an environmental stimulus after low-frequency (not noxious) repeated or prolonged exposure; increased intracellular Ca2+ during low-frequency stimulation activates small GTP-binding proteins that decrease the amount of vesicle release; does not occur in response to high frequency stimulation because high intracellular Ca2+ activates PKC, which inhibits the small GTP-binding proteins

sensitization

an increase in responsiveness to a stimulus as a result of repeated exposure to it or another stimulus; first stimulus recruits modulatory interneuron through an axon collateral; serotonin is released from an interneuron and activates the cAMP signaling pathway; serotonin receptor activates a G protein coupled receptor; when activated, potassium channel closes, which depolarizes the neuron and makes it more likely that the calcium channels will open; PKA increases vesicle release by blocking K+ channels and phosphorylating proteins that increase the probability of release

alpha SNAP

protein that forms around CORE complex to reverse vesicle release

NSF

ATPase that untangles CORE proteins, binds to ends of alpha SNAP

endosomes

pieces of plasma membrane that have been brought back in, budded off, and formed new vesicles

acidic

relative pH level of inside synaptic vesicles

coated pits

protein covered areas of cell surface that form as the vesicles combine with membrane adjacent to active zone but not in it

clathrin-mediated endocytosis

proteins identify portions of the membrane to be endocytosed; once a vesicle fuses and collapses into plasma membrane, synaptotagmin becomes associated with plasma membrane while still bound to calcium; coated ball of membrane pinches off into the cell

AP2

protein that associates with calcium bound synaptotagmin and is then associated with clathrin

PIP2

protein involved in clathrin-mediated endocytosis but exact purpose not known; cleaved in two by PLC to form IP3 and DAG

triskelion complex

ball of membrane formed by clathrin molecules

dynamin

GTPase that hydrolyzes GTP into GDP and therefore changes conformation to pinch off clathrin-coated vesicle

GTP gamma s

non hydrolysable form of GTP; when used, vesicles cannot be pinched off; when used, G protein is permanently activated

bulk endocytosis

large chunks of membrane brought back into the cell; demonstrated experimentally but may not happen physiologically

syndapin

protein involved in bulk endocytosis that is associated with actin filaments in the cytoskeleton, keeping it stabilized

kiss and run endocytosis

vesicle comes up, releases a little transmitter into the cell, and goes away; occurs in less active synapses; get fusion pore between vesicle and plasma membrane; combination of exocytosis and endocytosis happening all at once

ready pool

group of vesicles that are docked and just need calcium to be primed for exocytosis

recycle pool

group of vesicles that take the place of the ready pool once they are released; 10-20% of vesicles)

reserve pool

group of vesicles that have neurotransmitter in them but are otherwise not ready for release (do not have necessary proteins for exocytosis); 80% of vesicles; large backup to overcome vesicle depletion

synapsin

protein that can be phosphorylated, which determines affinity with which cytoskeleton binds to reserve pool vesicles; when phosphorylated, there is reduced affinity of vesicle for cytoskeleton which causes some of the reserve pool to move into the recycle pool

tetanus

bacteria releases a toxin that disinhibits alpha motor neurons allowing them to fire at high rates causing muscle spasms; also attacks VAMP

botulism

toxin that attacks cleavage sites on different proteins, which disrupts formation of the CORE complex and leads to a major decrease in neurotransmitter release; toxin taken up through endocytosis, then light chain gets spit out of vesicle and is free to go cleave proteins

ionotropic receptors

ligand-gated ion channels with rapid onset and termination of effects, 1:1 relationship between action and response, effects limited by type of channel, often bind neurotransmitters in the 1micrometer range, and often located near site of neurotransmitter release

metabotropic receptors

G-protein-coupled receptors with slow onset and termination of effects, >1:1 relationship between action and response due to amplification of protein cascade, diverse range of effects due to second messenger signaling pathways, often bind neurotransmitters in the 1nanometer range, and often located some distance from site of neurotransmitter release

pentameric

cys loop ionotropic receptor family;  nAchRs, serotonin, GABA-A, glycine

glutamate

tetrameric receptor family; NMDA, AMPA

trimeric

receptor family including ATP (P2X), ASIC (H+)

TRP receptor family

tetrameric receptor family best known for signaling in pain pathways

M2

transmembrane segment of nAChr that forms pore lining

alpha subunit

part of nAChR that contains binding site; requires 2 molecules of ACh to open; each nACR must contain at least two

Kd

dissociation constant; the concentration of a ligand at which 50% of receptors are occupied (have a ligand bound to them); inversely related to binding affinity; higher (so lower binding affinity) in muscarinic nAChRs than in neuronal

agonist

a compound that elicits the same biological effects as the endogenous (naturally occurring) ligand when it binds to a receptor

antagonist

a compound that reduces or eliminates the effect of an agonist when bound to a receptor

competitive antagonist

binds to the same site as an agonist (orthosteric binding) but does not activate the receptors; this reduces or prevents activation of the channel by an agonist

non-competitive antagonist

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binds to the receptor at a different site from an agonist (allosteric binding) but prevents or reduces activation of the receptor; referred to as a NAM (negative allosteric modulator)

reversible antagonist

binds non-covalently to the receptor, so can come off the receptor by “washing off”

irreversible antagonist

binds covalently to the receptor, so cannot be displaced by either competing ligands or “washing off”

GABA-B

metabotropic GABA receptors

GABA-A

inhibitory ligand-gated chloride channels in the pentameric receptor family; at resting potential, chloride moves into cell to create hyperpolarization

hyperpolarizing inhibition

reversal potential for GABA is equal to equilibrium potential for chloride (-70mV) so if membrane potential is more negative than -70, chloride moves out of cell

shunting inhibition

inhibition due to the fact that there is an additional pathway for ions to go through (GABA-A receptor); reduction in effect of excitatory neurotransmission

glycine receptor

member of pentameric receptor family that opens faster and desensitizes faster (quick peak); can sometimes have GABA and glycine being released from the same vesicle

seven

number of metabotropic receptor subunits

GDP

exchanged for GTP to cause activation of the G-protein

G alpha

protein bound to GDP and then GTP; transducer for primary effector

RGS

proteins that are not effectors and whose only purpose is to terminate action of G protein signaling; inhibit these to slow down hydrolysis

GDP-beta-S

form of GDP with a high affinity for alpha subunit, so cannot be swapped out for GTP and therefore G protein remains inactivated

antisense oligonucleotide

prevents translation of mRNA into protein

macromolecular complexes

groups of proteins that spatially segregate signaling cascades

amino terminal domains

most extracellular parts of ionotropic glutamate receptors

carboxy terminal domains

most intracellular parts of ionotropic glutamate receptors

AMPA receptor

ionotropic glutamate receptor with low conductance, fast gating speed, permeable to Na+, K+, and sometimes Ca2+, and no Mg2+ block

NMDA receptor

ionotropic glutamate receptor with high conductance, slow gating speed, permeable to Na+, K+, and Ca2+, and has Mg2+ block

glycine

inhibitory neurotransmitter less common than GABA that is a co-agonist at NMDA receptors

transducer

G protein (usually alpha but can be beta gamma) that activates primary effector and causes molecular switch from extracellular first messenger into an intracellular signaling event

primary effector

first protein that an alpha GTP or beta gamma dimers bind to; first thing specific to individual signaling pathway

GIRK channel

G protein inward rectifying potassium channel; modulated by beta gamma

direct pathway

G protein: beta gamma, primary effector: GIRK channels

Gs

stimulating G protein

adenylyl cyclase

primary effector of cAMP pathway; converts ATP to cAMP

cAMP

second messenger of cAMP pathway; activates PKA by binding to regulatory subunits

PKA

secondary effector of cAMP pathway; kinase that phosphorylates to increase probability of vesicle release during sensitization; found in in loop I/II in voltage-gated calcium channels

phospholipase C

primary effector of phosphoinositol pathway; protein that cleaves lipids, such as PIP2 into IP3 and DAG

IP3

second messenger of phosphoinositol pathway; receptors in the ER cause release of calcium into cytoplasm from ER (which activates PKC)

DAG

second messenger of phosphoinositol pathway; activates PKC

PKC

secondary effector of phosphoinositol pathway; phosphorylates calcium channels to decrease opening probability like in habituation; found in loop III/IV in voltage-gated calcium channels

PLA2

primary effector in arachidonic acid pathway; cleaves one tail off PIP2

arachidonic acid

second messenger in arachidonic acid pathway; the tail cleaved off PIP2 that can bind to things or be acted on by enzymes