GABA Receptor (GABAaR) Flashcards Preview

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Flashcards in GABA Receptor (GABAaR) Deck (11):
0

Superfamily

Pentametric Ligand-gated ionotropic receptors

1

Structure

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

2

Agonist

GABA

3

Function

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

4

Mutation

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

5

Bicuculline

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.

6

Benzodiazepine site

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).

7

Barbiturate site

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

8

Steroid site

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

9

Picrotoxin site

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.

10

Inverse agonist (negative agonist) site

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