title: Selective potentiation of alpha 1 glycine receptors by ginkgolic acid.
abstract: Glycine receptors (GlyRs) belong to the superfamily of pentameric cys-loop receptor-operated channels and are involved in numerous physiological functions, including movement, vision, and pain. In search for compounds performing subunit-specific modulation of GlyRs we studied action of ginkgolic acid, an abundant Ginkgo biloba product. Using patch-clamp recordings, we analyzed the effects of ginkgolic acid in concentrations from 30 nM to 25 μM on α1-α3 and α1/β, α2/β configurations of GlyR and on GABAARs expressed in cultured CHO-K1 cells and mouse neuroblastoma (N2a) cells. Ginkgolic acid caused an increase in the amplitude of currents mediated by homomeric α1 and heteromeric α1/β GlyRs and provoked a left-shift of the concentration-dependent curves for glycine. Even at high concentrations (10-25 μM) ginkgolic acid was not able to augment ionic currents mediated by α2, α2/β, and α3 GlyRs, or by GABAAR consisting of α1/β2/γ2 subunits. Mutation of three residues (T59A/A261G/A303S) in the α2 GlyR subunit to the corresponding ones from the α1 converted the action of ginkgolic acid to potentiation with a distinct decrease in EC50 for glycine, suggesting an important role for these residues in modulation by ginkgolic acid. Our results suggest that ginkgolic acid is a novel selective enhancer of α1 GlyRs.
authors.affiliation: Aix Marseille Université, INS UMR_S 1106 Marseille, France ; INSERM, UMR_S 1106 Marseille, France ; Department of Cytology, Bogomoletz Institute of Physiology Kyiv, Ukraine.
authors.forename: Galyna
authors.initials: G
authors.lastname: Maleeva
authors.affiliation: Aix Marseille Université, INS UMR_S 1106 Marseille, France ; INSERM, UMR_S 1106 Marseille, France.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Buldakova
authors.affiliation: Aix Marseille Université, INS UMR_S 1106 Marseille, France ; INSERM, UMR_S 1106 Marseille, France.
authors.forename: Piotr
authors.initials: P
authors.lastname: Bregestovski
keywords: CHO cells; glycine receptor; ion currents; ligand-gated channels; patch clamp; whole-cell recording