Module 2 Lecture 5

Question 1

how is diversity of GluAs increased

Answer 1

through post-transcriptional mechanisms

Question 2

what kind of modifications do AMPA receptors undergo

Answer 2

post-transcriptional, pre-translational
- nRNA editing
- alternative splicing

Question 3

what does alternative splicing affect in AMPA subunits

Answer 3

rate of desensitization
- controls whether flip or flop is expressed

Question 4

do flops or flips tend to desensitize faster

Answer 4

flops

Question 5

what does mRNA editing alter

Answer 5

Ca2+ permeability

Question 6

what happens if glutamine is changed to an arginine in GluA2 subunits

Answer 6

gets rid of Ca2+ permeability (goes from nonpolar to a positive residue)
- nearly 100% of GluA2 subunits have undergone this editing & are impermeable to Ca2+

Question 7

what are the differences in postsynaptic currents produced by

Answer 7

AMPA and NMDA receptors
- AMPA receptor EPSCs are fast and large
- NMDA receptor EPSCs are slower and smaller

Question 8

NMDAR structure

Answer 8

similar to AMPAR
- additional binding sites for co-agonist glycine and an extracellular Ca2+ binding site/pocket

Question 9

what determines how long the NMDAR channel stays open

Answer 9

subunit composition

Question 10

what subunit is required for form a functional NMDAR

Answer 10

GluN1
- other subunits affect the kinetics of gating

Question 11

what subunit composition of NMDAR is expressed early in development

Answer 11

NR1a/NR2D

Question 12

what subunit composition of NMDAR is expressed in adulthood

Answer 12

NR1a/NR2A

Question 13

what ions do NMDAR conduct

Answer 13

Na+, K+, and Ca2+

Question 14

what does NMDAR require to open

Answer 14

glutamate and co-agonist glycine (glycine usually present)

Question 15

what is NMDAR blocked by, and when

Answer 15

by Mg2+ ions at hyperpolarized potentials (if they open at negative membrane potential), and at rest

Question 16

what does excessive NMDAR activity cause

Answer 16

brain damage during stroke

Question 17

implications of NMDAR activity

Answer 17

synaptic plasticity, learning & memory

Question 18

NMDAR antagonist

Answer 18

ketamine

Question 19

what two conditions are required for NMDAR to open

Answer 19

1. bind glutamate
2. intracellular depolarization (such as from another input causing depolarization/action potentials)

Question 20

when does Mg2+ pop off NMDAR

Answer 20

when voltage inside the cell increases

Question 21

what happens if glutamate is released onto a weak synapse with an NMDAR

Answer 21

the glutamate binds to both AMPA and NMDA receptors, but only the AMPA receptors pass current, bc the NMDA receptors are blocked by Mg2+
- Na+ entry through AMPA receptors generates some depolarization, but not enough to trigger an AP< and not enough to unblock Mg2+ from the NMDAR

Question 22

role of presynaptic axon in AMPAR and NMDAR

Answer 22

stimulation causes pre-synaptic AP, trigger glutamate release from terminal

Question 23

what happens if glutamate is released onto a weak synapse with an NMDA receptor but there is a coincident strong input elsewhere

Answer 23

evoked depolarization of the neuron by the stronger synapse kicks the magnesium block off the NMDA receptor at the weak synapse, at the same time that the NMDA receptor is binding glutamate
- the NMDA receptor can now pass current, and it allows Ca2+ to enter the neuron

Question 24

are NMDA receptors and AMPA receptors at the same or different synapses?

Answer 24

some synapses only have AMPA, some have both AMPA and NMDA, some only have NMDA (silent synapses)

Question 25

what is a silent synapse

Answer 25

can receive signals, but they can't convert them into current - putting AMPA receptors on them = not silent anymore

Question 26

how is the Mg2+ block released

Answer 26

depolarization of the postsynaptic neuron by activation of AMPA receptors at the same time and neighboring synapses

Question 27

what does activation of NMDARs cause

Answer 27

Ca2+ influx

Question 28

what does Ca2+ do in metabotropic signaling

Answer 28

activates intracellular signaling pathways

Question 29

types of second messengers

Answer 29

Ca2+, cyclic AMP, cyclic GMP, IP3, diacylglycerol

Question 30

sources of Ca2+

Answer 30

plasma membrane, endoplasmic reticulum

Question 31

sources of Ca2+ in the plasma membrane

Answer 31

- voltage-gated Ca2+ channels - various ligand-gated channelss

Question 32

sources of Ca2+ in the endoplasmic reticulum

Answer 32

- IP3 receptors - ryanodine receptors

Question 33

intracellular targets for Ca2+

Answer 33

calmodulin, protein kinases, protein phosphates, ion channels, synaptotagmins, many other Ca2+ binding proteins

Question 34

Ca2+ removal mechanisms in the plasma membrane

Answer 34

Na+/Ca2+ exchanger, Ca2+ pump

Question 35

Ca2+ removal mechanisms in the endoplasmic reticulum

Answer 35

Ca2+ pump

Question 36

cyclic AMP source

Answer 36

adenylyl cyclase acts on ATP

Question 37

cyclic AMP intracellular targets

Answer 37

protein kinase A, cyclic nucleotide-gated channels

Question 38

cyclic AMP removal mechanisms

Answer 38

cAMP phosphodiesterase

Question 39

cyclic GMP sources

Answer 39

guanylyl cyclase acts on GTP

Question 40

cyclic GMP intracellular targets

Answer 40

protein kinase G, cyclic nucleotide-gated channels

Question 41

cys-loop receptors

Answer 41

nAChR, GABAA, glycine, and 5-HT3 - usually heteropentameric

Question 42

M2 p-loop receptors

Answer 42

AMPAR and NMDAR - usually heterotetrameric

Question 43

what superfamily do most GPCRs belong to

Answer 43

hepptahelical superfamily

Question 44

characteristics of GPCR subtypes/subunits

Answer 44

- 7 TM alpha helical regions - very highly conserved across related subtypes - mostly exist as monomers (some can be found as homo or heterodimers; mGluR always a dimer, GABAB always a heterodimer with one of each subtype)

Question 45

subunits of GABAB

Answer 45

heterodimer: one GABAB1 subunit and one GABAB2 subunit

Question 46

what happens when GPCR is bound by the appropriate ligand

Answer 46

the cytosolic surface undergoes a conformational change, usually due to movement of the sixth TM region further to the inner side of the membrane - allows G proteins to bined

Question 47

what do mGluR and GABAB dimers have that's similar to the ionotropic GluR clamshell

Answer 47

a venus flytrap domain at their N-terminals

Question 48

what does binding of 2 glutamate or 1 GABA to the GABAB1 subunit flytrap cause

Answer 48

a conformational shift and G-protein binding

Question 49

heterotrimeric G-protein subunits

Answer 49

alpha, beta, gamma

Question 50

characteristics of G-protein alpha subunits

Answer 50

can bind GDP or GTP

Question 51

what does GDP binding lead to in a GPCR

Answer 51

binding to beta and gamma to form a trimer/G-protein

Question 52

what happens when GPCRs bind their ligand

Answer 52

g-proteins bind, allowing GTP to replace GDP

Question 53

what happens when GTP replaced GDP

Answer 53

dissociation and allows the activated alpha or beta-gamma subunits to affect effector proteins and other molecules

Question 54

GTPase-activating protein function (GAPs)

Answer 54

inactivate G-proteins

Question 55

what is the function of the amplification of signalizing cascades

Answer 55

allow GPCRs to produce long-lasting and varied effects

Question 56

transmitter role in GPCR

Answer 56

binds to receptor

Question 57

receptor role in GPCR

Answer 57

activated G protein

Question 58

G protein role in GPCR

Answer 58

alters activity of effector molecule

Question 59

effector molecule role in GPCR

Answer 59

changes concentration of second messenger

Question 60

second messenger role in GPCR

Answer 60

modulates activity of enzyme, and modulates activity of target - affect the rates at which kinases and phosphatases phosphorylate proteins

Question 61

enzyme role in GPCR

Answer 61

modulates activity of target

Question 62

what does upregulation of CREB do

Answer 62

crucial for many cellular processes, including memory formation