GABA Receptor (GABAaR)

Question 0

Structure

Answer 0

4 helical transmembrane spanning segments, 15 different subunits in 7 families - various subunit combination may determine the regulation of Cl influx, etc.

Question 1

Superfamily

Answer 1

Pentametric Ligand-gated ionotropic receptors

Question 2

Agonist

Answer 2

GABA

Question 3

Function

Answer 3

Binds major inhibitory transmitter GABA in the CNS. Regulates neuronal responses by conducting Cl influx via activated GABAaR/Cl channels inducing membrane hyperpolarization
* prevents AP

Question 4

Mutation

Answer 4

Mutation of GABAaR can results in severe neurodegenerative diseases such as Huntington’s, epilepsy, and alcoholism

Question 5

Bicuculline

Answer 5

A GABAaR blocking, selective/competitive GABAaR antagonist.

• Prevents the opening of Cl channels, allowing the passage of neuronal responses.
• Can be a convulsant that induces convulsions and/or epileptic seizures.

Question 6

Benzodiazepine site

Answer 6

A positive allosteric (modulatory) site on the GABAaR
Tranquilizers: diazepam, chlordiazepoxide, lorazepam, and alprazolam bind to this site to INCREASE GABAaR affinity for binding with GABA (acts to increase the frequency of Cl channel opening)
*Used as a sedative, anxiolytic, anticonvulsant, and muscle relaxant (opposite to bicuculline).

Question 7

Barbiturate site

Answer 7

target for some sedative-hypnotics and anesthetics including barbiturates (phenobarbitol, pentobarbitol), ethanol, and volatile anesthetics (chloral hydrate and enflurane). They increase the duration of Cl channel openings/decrease the likelihood of short-lived opening without affecting the frequency of Cl opening - maximizes Cl flow in the cell

Question 8

Steroid site

Answer 8

Target for some anesthetics that potentiate GABAaR mediated IPSPs (Cl influx induced membrane hyperpolarization) = calming and sedation

Question 9

Picrotoxin site

Answer 9

Blocked by non-competitive GABAaR antagonist picrotoxin (pentylenetetrazol) which does not bind directly to the GABA-binding site. Blockage of this site decreases Cl channel activity.

Question 10

Inverse agonist (negative agonist) site

Answer 10

beta-carboline (monoamine oxidase inhibitor) binds to the allosteric benzodiazepine site, decreasing the efficiency of GABA binding and Cl channel opening = decrease in GABAaR fxn.
* Can induce convulsion, anxiogenic, and memory enhancing effects