Conformational specificity of GABA binding to the presynaptic GABAA receptor.
GABAA receptors on the synaptic terminal of retinal bipolar neurons mediate the inhibition by GABA of presynaptic calcium influx in these non-spiking interneurons. To characterize the conformational specificity of GABA binding to the receptor underlying this presynaptic inhibition, we have recorded the conductance change induced in isolated bipolar cells by GABA and by two conformationally locked analogs of GABA, cis- and trans-4-aminocrotonic acid (ACA). Trans-ACA (the extended conformation) is more potent than GABA in activating the GABAA chloride conductance of the synaptic terminal, while cis-ACA (the folded conformation) is 20-fold less potent than GABA. These results show that the extended conformation of GABA is the preferred form for the presynaptic GABAA receptor.
Ayoub
G S
GS
Department of Neurobiology & Behaviour, State University of New York, Stony Brook 11794-5230.
Matthews
G
G
D000818:Animals; D002712:Chlorides / Q000502:physiology; D003437:Crotonates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D011963:Receptors, GABA-A / Q000378:metabolism*; D013237:Stereoisomerism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002712:Chlorides; D003437:Crotonates; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid