AMINOACID RESIDUES INVOLVED IN POSITIVE MODULATION OF αl GLYCINE RECEPTORS BY GINKGOLIC ACID.

Abstract

Previously, we have shown that ginkgolic acid has an ability to potentiate currents, mediated by αl subunits of glycine receptor. In order to define the mechanism of subunit specific action of ginkgolic acid we have performed comparative analysis of the amino acid sequences of at and α2 subunits of glycine receptor. Amino acids that contribute to the different action of ginkgolic acid on glycine receptors formed by these subunits were determined. Using whole-cell configuration of patch-clamp recording, we have demonstrated that mutation of three residues in α2 subunit for corresponding ones from αl subunit makes α2 receptors sensitive to the potentiation by ginkgolic acid. Currents, mediated by α2 mutant receptors, increased by 89±14% after application of ginkgolic acid. Similarly to ai receptors α2 mutant receptors have shown a decrease in EC₅₀. for glycine under the action of ginkgolic acid. Thus, subunit selectivity of the ginkgolic acid is in strong connection with three amino acid residues that are different in α1 And α2 subunits of glycine receptor.