The GABA(A) receptor is a ligand-gated chloride-ion channel responsible for mediating the effects of Gamma-AminoButyric Acid (GABA), the major inhibitory neurotransmitter in the human body.
The receptor is a multimeric transmembrane receptor that sits in the membrane of its neuron. Once bound to its ligand, the protein receptor changes confirmation within the membrane. This particular protein is configured in such a way as to allow certain ions to pass through its pore when the pore is open. The ligand GABA is the endogenous compound that tells this receptor to open, allowing chloride ions (Cl-) to pass down its electrochemical gradient . Because the chloride ion concentration is high outside of the cell, opening of the channel pore results in an influx of chloride into the cell, thus hyperpolarizing it.
Other ligands interact with the GABA(A) receptor to mimic GABA or to potentiate its response. Such other ligands include the benzodiazepines (increase pore opening frequency), barbiturates (increase pore opening duration), and certain steroids. Still other compounds interact with the GABA(A) receptor to attenuate the effects of GABA; such blocking agents are Flumazenil (a competitive benzodiazepine antagonist) and picrotoxin, which blocks the channel directly.
The phenotypic response to all of these interactions is seen in effects such as muscle relaxation, sedation, anticonvulsion, and anesthesia, based on the location of the cell in question, its intracellular second-messenger milieu, and the dose of the ligand at the receptor; the dosage issue is commonly related to the amount of exogenous drug that is delivered to the patient (e.g., anesthesia during surgery).
External links
Basic Neurochemistry: GABA Receptor Physiology and Pharmacology
