Ionotropic/metabotropic Receptors

Question 0

Inward current produces a _____ deflection?

Answer 0

Downward

Question 1

Current is a measure of ion flow in what direction?

Answer 1

Direction of POSTITIVE ion

Opposite direction to -ve ion

Question 2

Membrane potential (EPSP/IPSP) is a __________ of the current (EPSC)?

Answer 2

Mirror image

Question 3

IONOTROPIC receptors consist of how many subunits?

Answer 3

4 or 5

Question 4

Which subunits of the nAChR have the ACh binding sites?

Answer 4

2 alpha subunits

Question 5

The transmembrane domains of each subunit are arranged so that which domain forms the pore?

Answer 5

TM2

Question 6

Each TM2 has what that forms the selectivity filter?

This makes nAChR selective to____?

Answer 6

Negatively charged AAs

cations

Question 7

How do muscle and brain nAChRs differ?

Answer 7

1) SUBUNITS: - muscle has 2a, B, d, y or E.
- brain 3a, 2B or 5a

2) Muscle nAChR binds alpha BUNGAROTOXIN, brain does not

Question 8

Other than nACh what other IONOTROPIC receptors are there (7)?

Answer 8

AMPA, NMDA, kainate, 5-HT, purines, GABA, glycine

Question 9

What are the 3 types of IONOTROPIC glutamate receptors and their possible subuints?

Answer 9

NMDA (NMDAR1, NMDAR2a-d, NMDAR3a-b)

AMPA (GluR1-4)

Kainate (GluR5-7, KA1, KA2)

Question 10

How many subunits do ionotropic glutamate receptors have?

Answer 10

4

Tetramers

Question 11

What is the major receptor for excitatory transmission?

Answer 11

AMPA

Question 12

What is the structure of an AMPA receptor?

What are the two most common conformations?

Answer 12

Dimer or dimers

GluR1/GluR2: -most common, allows Na+ to pass. GluR2 controls Ca permeability, prevents Ca entry

GluR1/GluR1: - formed due to activity/insult. Allows passage of Na and Ca => larger depolarization (+ Ca acts as 2nd messenger)

Question 13

What stimulates an increase in expression of AMPA receptors (esp GluR1 hetromer) in postsynaptic membrane?

Answer 13

Lots of synaptic activity

Question 14

What is the subunit composition of an NMDA receptor?

Answer 14

2 x NR1 (glycine)
2x NR2 (glutamate)

Question 15

What is the role of glycine in NMDA receptor?

Answer 15

Co-agonist

Need both glut and glyc to open channel

Question 16

What ions does the NMDA receptor allow to pass when open?

Why is the channel not open at resting potentials?

Answer 16

Na, Ca (and K)

Pore blocked by Mg2+

Question 17

NMDA receptor is known as a _______ detector?

Answer 17

Coincidence

Question 18

Explain why inward current of NMDA receptor is voltage-dependent

Answer 18

Resting potentials- pore blocked

Upon depolarization (due to AMPA activation) Mg2+ is forced out of pore, allowing influx of Na/Ca

NMDA activity needs high-frequency stimuli

Question 19

What is the Ca2+ entering NMDA (acting as 2nd messenger) important for?

Answer 19

Long term potentiation

important for learning and memory

Question 20

The function of which receptor is important for synaptic plasticity?

Answer 20

NMDA

Question 21

Describe the current through an AMPA and NMDA receptor?

Answer 21

AMPA: rapid rise in current but v transient (dissipates quickly)

NMDA: slower activation, current doesn’t reach max, but sustained/lasts longer

Question 22

GABAa receptors have binding sites for _______ that change effect of GABA binding on the receptor?

Answer 22

Allosteric modulators

Question 23

What effect do benzodiazepines have on GABAa?

Answer 23

Potentiate GABA activity
Agonist
Increase frequency of channel opening

Question 24

What effect do barbiturates have on GABAa?

Answer 24

Agonist Increase binding of GABA and benzodiazepines Increase time channel open (increased Cl- flux)

Question 25

Steroids have similar effect on GABAa as_____?

Answer 25

Barbiturates

Question 26

What effect do picrotoxins have on GABAa?

Answer 26

Inhibit channel Acts on gating process Decreases time channel open

Question 27

What allosteric modulator binding sites are located in the pore of GABAa?

Answer 27

Barbiturates, steroids, picrotoxin

Question 28

How many subunits form GABAa? Which subunits have GABA binding sites?

Answer 28

5 (pentameric) B subunits

Question 29

What is the common structure of metabotropic receptors? What are exceptions to this?

Answer 29

Monomeric Glutamate and GABA receptors = dimers

Question 30

G proteins are _____ proteins?

Answer 30

Trimeric

Question 31

Which G protein subunit binds GDP and interacts with GPCR?

Answer 31

Alpha

Question 32

What happens upon activation of a G-protein when it interacts with GPCR?

Answer 32

GDP replaced by GTP a subunit dissociates from By subunits

Question 33

How do G-protons return to inactive state?

Answer 33

a subunit hydrolyses GTP to GDP a re associates with By

Question 34

What is special about GTP-y-s which binds G proteins?

Answer 34

Can't be hydrolysed | Subunits remain active

Question 35

Give 8 metabotropic receptor classes

Answer 35

Glutamate, GABAb, histamine, 5-HT, purines, dopamine, NA/Ad, muscarinic

Question 36

How many classes/groups of mGluRs (mGluR1-7) are there? Which receptor subtypes are in each class?

Answer 36

3 Group I: mGluR1 + mGluR5 Group II: mGluR2 + mGluR3 Group III: mGlurR4,6,7,8

Question 37

Group I mGluRs are coupled to which type of G protein? And located mostly pre or post synaptic?

Answer 37

Gq (PLC -> DAG + IP3 -> PKC + Ca -> increased protein phos + activated Ca binding proteins) Postsynaptic

Question 38

Group II mGluRs are coupled to which type of G protein? And located mostly pre or post synaptic?

Answer 38

Gi (inhibits ad cyc and cAMP -> decreased pka an decreased protein phos) Presynaptic

Question 39

How are mGluRs modulatory?

Answer 39

Modulate neurone and determine future cell response | Make cell more or less likely to fire

Question 40

How specifically are group I mGluRs modulatory ?

Answer 40

Gq -> PKC PKC modulates AMPA receptors, internalises receptors so glut can't bind Can't contribute to future EPSPs, less likely to be excited

Question 41

What is the modulatory effect of group II mGluRs?

Answer 41

Gi -> inhibit cAMP Reduce NT release

Question 42

GABAb is a hetrodimer. Which monomer binds GABA?

Answer 42

R1

Question 43

Activation of GABAb is inhibitory, how?

Answer 43

Coupled to Gi Decreased protein phosphorylation Increased k+ channel activity (hyper polarises cell) Inhibits Ca channels (less Ca influx = less NT release)