GABA-a Receptor
Definition
The main inhibitory ligand-gated ion channel in the CNS; a pentameric alpha-beta-gamma subunit complex that opens its central chloride channel when GABA binds the orthosteric site. Benzodiazepines bind at the alpha-gamma interface to increase chloride channel opening frequency.
- Role
- Main inhibitory ligand-gated ion channel in the CNS
- Structure
- Pentameric alpha-beta-gamma subunit complex
- Channel type
- Central chloride channel
- Benzodiazepine binding site
- Alpha-gamma subunit interface
Common questions
Why do benzodiazepines and barbiturates both act at this receptor but produce different effects?+
Benzodiazepines bind at the alpha-gamma interface and increase how often the chloride channel opens in response to GABA, while barbiturates bind elsewhere and increase how long the channel stays open per opening, and at high doses barbiturates can open the channel even without GABA present, which is why barbiturate overdose is more dangerous.
How does GABA-A receptor pharmacology explain benzodiazepine-barbiturate cross-tolerance in overdose cases?+
Because both drug classes converge on potentiating the same chloride channel, chronic use of one produces receptor adaptations that blunt the effect of the other, which toxicologists factor into interpreting blood concentrations against a person's tolerance history in fatality cases.
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