GABA receptors

Question 1

What receptor is this?

G0 beta/gamma complex component inhibits calcium entry at presynaptic terminal and therefore causes autoinhibition by lowering neurotransmitter release upon second stimulation.

Answer 1

GABA-b receptor

Question 2

what receptor is this?
Gi beta/gamma complex facilitates opening of K channels
- hyperpolarization of postsynaptic membrane and therefore direct synaptic inhibition

Answer 2

Postsynaptic, metabotropic GABAb receptor

Question 3

what occurs if EPSP precedes IPSP?

Answer 3

no effect on on EPSP– normal excitation

Question 4

what occurs if IPSP precedes EPSP

Answer 4

inhibitory effect— EPSP is abolished

Question 5

Barbiturate, benzodiazepines are:
- enhancers or inhibitors?
- bind the different/same sites on GABAaR?

Answer 5

• enhance receptor function
• bind different sites

Question 6

Drugs that enhance GABAa receptor function are known as what?

examples
anxiolytic, anticonvulsant, analgesic, sedative, amnestic

Answer 6

positive allosteric modulators (PAMS)

Question 7

pro-convulsant, anxiogenic drugs are characteristic to what kind of GABAa receptor drugs

Answer 7

GABAa inhibitors

Question 8

how do benzodiazepines enhance GABAa receptors?

Answer 8

increase channel opening probability

Question 9

mechanism of barbiturates on GABAa receptor enhancement?

Answer 9

• longer duration channel opening
• direct receptor activation at high barbiturate concentration

Question 10

which GABAar enhancers can induce anesthetic “unconscious state?

Answer 10

• propofol, etomidate, barbiturates

NOTE: benzodiazepines do NOT

Question 11

effect of Picrotoxin, bicuculline on GABAa receptor?

Answer 11

GABAar blockers

Question 12

a1b1 GABAar and their response to (activation/no effect):
- GABA
- benzodiazepine
- Bicuculline
- picrotoxin

Answer 12

• enhanced
• enhanced (A1 has H101)
• inhibited
• inhibited

Question 13

what is the determining characteristic of DIAZEPAM sensitive GABAaRs (i.e. GABAa1-5 are sensitive) ?

Answer 13

• H residue at position 101

ex. A1-5 are sensitive (have H101)

Question 14

what do GABAa recpetor subtypes A4,A6 have in common? (think in terms of DIAZEPAM sensitivity?)

Answer 14

• not sensitive to DIAZEPAM
• have R instead of H at position 101

Question 15

result of R101 mutation to H (in terms of diazepam sensitivity)?

Answer 15

receptor becomes sensitive

Question 16

result of A1H101R knock-in in mice? (in terms of diazepam sedative/anxiolytic effects)
- what does this say about the function of A1 beta/gamma receptor

Answer 16

• diazepam no longer sedative
  still anxiolytic

suggests sedative effects is mediated by A1 beta/gamma2 receptors

Question 17

effect of diazepam on A2H101R mouse knock in (in terms of diazepam sedative/anxiolytic effect)

what does this tell us about A2?

Answer 17

• No longer anxiolytic
• remains sedative
• potential drug target for anti-anxiety medication

Question 18

Resulting etomidate effect on Beta2 N265S mutation (in terms of GABAaR enhancement/sedative/hypnotic)?

Answer 18

• reduced GABAa receptor enhancement
• lowered sedative effects
• impaired hypnotic action

Question 19

effect of etomidate/propofol on Beta3 N265M mutation ( in terms of GABAa enhancement/hypnotic action)?

Answer 19

• reduced GABAaR enhancing effects
• greatly impaired hypnotic action

Question 20

alpha1 GABAa receptor isoform mediates what Benzodiazepine behavior?

Answer 20

sedation

Question 21

What GABAa receptor isoform(s) mediate anxiolytic/analgesic behavior?

Answer 21

• Alpha2
• Alpha3

Question 22

beta3 subunit mediates what benzodiazepine effect?

Answer 22

• anaesthesia/immobility

Question 23

beta2 subunit of GABAa receptor mediates what benzodiazepine behavior

Answer 23

• sedation/anaesthesia

Question 24

Alpha5 GABAa receptor isoform mediates what benzodiazepine effect?

Answer 24

• effect on cognition

Question 25

What residue (located in Transmembrane region 2 ) dictates beta subunit specificity in:
- Beta2,3
- Beta 1

Answer 25

• B2,3: Asparagine
  B1: Serine