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  • Title: The GABAA receptor: new insights from single-channel recording.
    Author: Mathers DA.
    Journal: Synapse; 1987; 1(1):96-101. PubMed ID: 2905528.
    Abstract:
    The GABAA receptor of mammalian neurons exists as a macromolecular complex incorporating several interacting components. These include a chloride-permeable ion channel and a recognition site for GABA. The binding of GABA molecules at the latter site triggers the transient opening of the chloride ion channel, resulting in a flow of charge which inhibits the generation of action potentials in the cell. The precise amount of charge passed during this event is modulated by ligand binding at at least three regulatory sites. These sites act as receptors for barbiturates, benzodiazepines, and certain convulsants. The extracellular patch clamp method has now been used to study the gating of chloride channels by GABA and the modulation of this process by drugs. Even in the absence of drugs, GABAA channels exhibit complex gating behavior, indicating the presence of multiple open and closed states and of substate conductance levels. GABAA channels from different preparations show considerable diversity in their detailed gating characteristics. In the presence of the barbiturate pentobarbital, GABAA channels open in prolonged bursts, consistent with the potentiating effect of this drug on macroscopic GABA responses. In contrast, the convulsant penicillin decreases charge transfer through open GABAA channels by shortening the average duration of the open state. Benzodiazepine receptor ligands exert complex effects on the GABAA channel. A general model of barbiturate and benzodiazepine potentiation of GABAA receptor responses is proposed.
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