GABA receptors Flashcards
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.
GABA-b receptor
what receptor is this?
Gi beta/gamma complex facilitates opening of K channels
- hyperpolarization of postsynaptic membrane and therefore direct synaptic inhibition
Postsynaptic, metabotropic GABAb receptor
what occurs if EPSP precedes IPSP?
no effect on on EPSP– normal excitation
what occurs if IPSP precedes EPSP
inhibitory effect— EPSP is abolished
Barbiturate, benzodiazepines are:
- enhancers or inhibitors?
- bind the different/same sites on GABAaR?
- enhance receptor function
- bind different sites
Drugs that enhance GABAa receptor function are known as what?
examples
anxiolytic, anticonvulsant, analgesic, sedative, amnestic
positive allosteric modulators (PAMS)
pro-convulsant, anxiogenic drugs are characteristic to what kind of GABAa receptor drugs
GABAa inhibitors
how do benzodiazepines enhance GABAa receptors?
increase channel opening probability
mechanism of barbiturates on GABAa receptor enhancement?
- longer duration channel opening
- direct receptor activation at high barbiturate concentration
which GABAar enhancers can induce anesthetic “unconscious state?
- propofol, etomidate, barbiturates
NOTE: benzodiazepines do NOT
effect of Picrotoxin, bicuculline on GABAa receptor?
GABAar blockers
a1b1 GABAar and their response to (activation/no effect):
- GABA
- benzodiazepine
- Bicuculline
- picrotoxin
- enhanced
- enhanced (A1 has H101)
- inhibited
- inhibited
what is the determining characteristic of DIAZEPAM sensitive GABAaRs (i.e. GABAa1-5 are sensitive) ?
- H residue at position 101
ex. A1-5 are sensitive (have H101)
what do GABAa recpetor subtypes A4,A6 have in common? (think in terms of DIAZEPAM sensitivity?)
- not sensitive to DIAZEPAM
- have R instead of H at position 101
result of R101 mutation to H (in terms of diazepam sensitivity)?
receptor becomes sensitive
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
- diazepam no longer sedative
still anxiolytic
suggests sedative effects is mediated by A1 beta/gamma2 receptors
effect of diazepam on A2H101R mouse knock in (in terms of diazepam sedative/anxiolytic effect)
what does this tell us about A2?
- No longer anxiolytic
- remains sedative
- potential drug target for anti-anxiety medication
Resulting etomidate effect on Beta2 N265S mutation (in terms of GABAaR enhancement/sedative/hypnotic)?
- reduced GABAa receptor enhancement
- lowered sedative effects
- impaired hypnotic action
effect of etomidate/propofol on Beta3 N265M mutation ( in terms of GABAa enhancement/hypnotic action)?
- reduced GABAaR enhancing effects
- greatly impaired hypnotic action
alpha1 GABAa receptor isoform mediates what Benzodiazepine behavior?
sedation
What GABAa receptor isoform(s) mediate anxiolytic/analgesic behavior?
- Alpha2
- Alpha3
beta3 subunit mediates what benzodiazepine effect?
- anaesthesia/immobility
beta2 subunit of GABAa receptor mediates what benzodiazepine behavior
- sedation/anaesthesia
Alpha5 GABAa receptor isoform mediates what benzodiazepine effect?
- effect on cognition
What residue (located in Transmembrane region 2 ) dictates beta subunit specificity in:
- Beta2,3
- Beta 1
- B2,3: Asparagine
B1: Serine
