Biophysical properties and regulation of GABAA receptor channels

When GABA binds to the GABA_A receptor, bursts of chloride ion channel openings occur, resulting in membrane hyperpolarization. Barbiturates increase current by increasing mean channel open time, and the convulsant drug picrotoxin decreases current by decreasing mean channel open time. The two drugs bind to allosterically coupled sites on the receptor to regulate channel gating. Benzodiazepines increase and β-carbolines decrease channel opening frequency by binding to the benzodiazepine receptor on GABA_A receptor channels. Neurosteroids increase current by increasing mean channel open time and opening frequency, possibly by interacting with a specific site on the GABA_A receptor. The convulsant drug penicillin reduces current by producing open channel block. The GABA_A receptor subunits contain consensus sequences for phosphorylation by cAMP-dependent kinase, C kinase and tyrosine kinase. The functional consequences of receptor phosphorylation remain unclear. In future studies the use of molecular biological and single channel recording techniques should allow characterization of the properties of GABA_A receptor channels, the role of receptor phosphorylation and the specific mechanisms of actions of regulatory drugs.