PSC2002/L14 Ligand Gated Channels

Question 1

Define neurotransmitters.

Answer 1

Chemical messengers released from one neuron and acting at a close site on another to elicit an effect determined by the specific nature of the receptor

Question 2

What is acetylcholine for?

Answer 2

Voluntary movement of muscles

Question 3

What is glutamate used for?

Answer 3

Major excitatory neurotransmitter
Roles in memory & learning

Question 4

What is dopamine for?

Answer 4

Motivation
Pleasure associated with addiction & love

Question 5

What is serotonin for?

Answer 5

Emotions, wakefulness
Temperature regulation

Question 6

What is GABA for?

Answer 6

Major inhibitory neurotransmitter

Question 7

What is ATP for?

Answer 7

Neuronal/glial communication, role in pain regulation

Question 8

Define endogenous agonists.

Answer 8

Ligands made in the body which cause a postsynaptic effect

Question 9

Describe ionotropic receptors.

Answer 9

Ligand-gated ion channels
Binding of neurotransmitter triggers opening of channel
Quickly changes electrical charge of a cell

Question 10

Describe metabotropic receptors.

Answer 10

GPCR
G-protein phosphorylation pathway
cAMP, IP3 or DAG

Question 11

How are ion channels best understood?

Answer 11

In terms of their reverse potentials

Question 12

Name 2 non-specific cation channels.

Answer 12

E(AChR)
E(glut)

Question 13

Describe synaptic transmission of ACh. (4)

Answer 13

Synthesis in cytoplasm by ChAT combining acetyl-CoA with choline
Depolarisation - AP reaches axon terminal
Calcium influx via VG Ca2+ channels
Vesicle fusion - release of ACh
Binding to ionotropic & metabotropic receptors

Question 14

Describe termination of ACh action.

Answer 14

AChE breaks down ACh into acetate and choline
Choline reuptake via choline transporter into postsynaptic membrane

Question 15

Describe recycling & resynthesis of ACh.

Answer 15

Choline combined with acetyl-CoA in presynaptic neuron to form more ACh

Question 16

Describe Loewi’s experiment (1936). (3)

Answer 16

2 frog heart preps with interconnected perfusion chambers
Stimulated one vagal nerve to slow heart rate
Effect also transferred to second heart

Question 17

Define a quanta.

Answer 17

Contents of one vesicle of neurotransmitter

Question 18

How does the smallest postsynaptic response arise?

Answer 18

From release of one vesicle’s contents

Question 19

What is a mini?

Answer 19

Postsynaptic response of a single vesicle released spontaneously

Question 20

Describe the evidence in termination of ACh transmission.

Answer 20

Persistent ACh application produces persistent current (not indefinitely; AChRs desensitise)
Q(10) - diffusion dominated processes have Q(10) = ~1
Voltage dependence of decay (faster at more negative holding potentials)

Question 21

Describe Neher and Sakmann’s patch clamping experiment. (3)

Answer 21

Glass pipette with fine tip to isolate and seal small patch of membrane
Pipette gently pressed against cell membrane, strong enough seal = tight connection (high-resistance seal
Measures small currents through ion channels without significant leakage or noise from rest of cell

Question 22

Where are nicotinic ACh receptors found?

Answer 22

NMJ (muscle cells)
Between pre & postsynaptic cells in ANS

Question 23

What are nicotinic ACh receptors permeable to?

Answer 23

Na+
K+
Ca2+
E(rev) = ~5mV

Question 24

What is the composition of nicotinic ACh receptors? Which subunit binds ACh?

Answer 24

2a, 1B, 1d, 1E
a subunits binds ACh (2 ACh bind per receptor)

Question 25

Give 2 antagonists of the nicotinic ACh receptor.

Answer 25

a-bungarotoxin (snake venom)
Curare compounds (plants)

Question 26

Describe myasthenia gravis and what 2nd subset is.

Answer 26

Autoimmune disease
Body produces autoantibodies against nicotinic ACh receptors
Membrane damage & decreased availability & number of AChRs
2nd subset - autoantibodies against Muscle Specific Kinase (MuSK)

Question 27

Which GABA and glycine receptors are:
a) ionotropic
b) metabotropic?

Answer 27

a) GABA(A&C), glycine
b) GABA(B)

Question 28

When are E(cl) and E(m) inhibitory?

Answer 28

Below action potential threshold (as they’re close together)

Question 29

Describe 5HT(3) receptors.

Answer 29

Pentamers
Similar transmembrane loops
Na+, K+, Ca2+ permeability (other 5HT-Rs are metabotropic)

Question 30

What is dictated by subunit composition in GABA-R? (3)

Answer 30

Receptor properties (sensitivity, conductance, kinetics of opening and closing)
Cell surface distribution
Dynamic regulation

Question 31

Describe the Met286 to Trp (BM286W) mutation to GABA(A) receptors.

Answer 31

Abolition of pentobarbital sensitivity of B2 receptor channel
In wild-type B2 receptor channel, markedly increased by coapplication of GABA and pentobarbital

Question 32

Describe modulation of synaptic receptors. (3)

Answer 32

Benzodiazepines (e.g., diazepam)
Mediate sedation
Bind at interface of a/y2 subunits

Question 33

Describe modulation of extrasynaptic receptors. (3)

Answer 33

Barbituates increase affinity of GABA
Neurosteroids both positive and negative allosteric modulation
Alcohol enhances GABA action

Question 34

Describe pharmacological modulation of GABA-Rs.

Answer 34

Modulators of GABAergic action
Make distinction between agonists and some drugs.

Question 35

What is the purpose of:
a) barituates
b) benzodiazepines?

Answer 35

a) ‘locks’ GABA receptors in open state
b) eases opening of receptors

Question 36

Describe P2X ionotropic receptor.

Answer 36

ATP agonist
Different structure to other channels
Na+, K+, Ca2+ permeable
Widespread glia and neuronal expression
ATP released in synaptic vesicles
Important means of neuronal to glial, glia-to-glia communication