ALLOSTERIC UNCOUPLING OF GABA AND BENZODIAZEPINE BINDING SITES INDUCED BY A SHORT TIME EXPOSURE TO GABA

MARIA CLARA GRAVIELLE

Mar del Plata

Simposio; Congreso satélite de la Reunión Anual de la International Society for Neurochemistry/ American Society for Neurochemistry: GABA receptors and calcium channels: effects on neuronal growth, plasticity and survival; 2001

International Society for Neurochemistry/ American Society for Neurochemistry

Chronic exposure of neurons to GABA induces down-regulation of receptor number and reduction in allosteric interactions among binding sites on the receptor complex, a phenomenon called uncoupling. The molecular mechanism underlying this regulation is not completely understood. In the present study we found that a short time exposure (5-10 min) of rat cortical neurons to GABA followed by a 48 h incubation period in the absence of agonist induced a decrease in GABA potentiation of benzodiazepine (BDZ) binding (46.59 +/- 6.05 % uncoupling) without a change in receptor number of affinity. This alteration in GABA-A receptor was correlated to a decrease in alpha1 (39.67 +/- 5.36 %) and beta2/3 (28.67 +/- 4.49 %) subunit protein levels. Analysis of mRNA levels indicated a significant reduction in alpha 1 (8.29 +/- 2.37 %), alpha 4 (17.14 +/- 6.90 %) and beta 1 (16.00 +/- 4.39 %) subunit mRNAs. However, no change was found in beta 2 and beta 3 subunit mRNAs. These results indicate that a short time incubation with GABA induces only uncoupling between GABA and BZD binding sites. The molecular mechanism involves regulation of transcription or mRNA stability and a post-transcriptional control for different subunits. This process might lead to a change in subunit composition of GABA-A receptor.