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.