AMINOACID RESIDUES INVOLVED IN POSITIVE MODULATION OF a1 GLYCINE RECEPTORS BY GINKGOLIC ACID
G. Maleeva1,2, S. Buldakova1, G. Skibo2, P. Bregestovski1
- Institute de Neurosciences des Systemes, INSERM UMR
1106, Aix-Marseille Université, France ;
- Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz62.05.019
Abstract
Previously, we have shown that ginkgolic acid has an ability
to potentiate currents, mediated by α1 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 α1 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
α1 subunit makes α2 receptors sensitive to the potentiation by
ginkgolic acid. Сurrents, mediated by α2 mutant receptors,
increased by 89±14% after application of ginkgolic acid.
Similarly to α1 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.
Keywords:
glycine receptor; ginkgolic acid; ionic currents; patch-clamp; point mutations.
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