GABA A receptor
From Freepedia
The GABAA 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 consists of five subunits arranged around a central pore. The receptor sits in the membrane of its neuron at a synapse. The ligand GABA is the endogenous compound that causes this receptor to open; once bound to GABA, the protein receptor changes conformation within the membrane, opening the pore in order to allow chloride ions (Cl-) to pass down their 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 making it more negative (hyperpolarizing it).
Other ligands interact with the GABAA 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, called neuroactive steroids. Still other compounds interact with the GABAA 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
Dr. Dreyer's GABA-R webpage (University of Fribourg, Switzerland)
