GABA_A Receptor

GABA_A Receptor

The GABA_A receptor (GABA_AR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABA_A receptor selectively conducts Cl- through its pore, resulting in hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring. The reversal potential of the GABAA-mediated IPSP in normal solution is -75 mV, contrasting the GABA_B IPSP.

The active site of the GABA_A receptor is the binding site for GABA and several drugs such as muscimol, gaboxadol, and bicuculline. The protein also contains a number of different allosteric binding sites which modulate the activity of the receptor indirectly. These allosteric sites are the targets of various other drugs, including the benzodiazepines, nonbenzodiazepines, barbiturates, ethanol, neuroactive steroids, inhaled anaesthetics, and picrotoxin, among others.

Mild inhibition of neuronal firing by drugs acting at the GABA_A receptor causes a reduction of anxiety in the patient (an anxiolytic effect) while more pronounced inhibition induces general anesthesia. An extreme overdose is very rare and will induce anesthesia for an extended period of time, in many cases the patient can sleep for days, weeks, months, years, or even die.