Molecular Sites for the Positive Allosteric Modulation of Glycine Receptors by Endocannabinoids
Figure 6
The negative allosteric effects of NA-Gly on α3 GlyRs were attenuated but not reverted by altering the TM2 domain composition.
(A) Primary sequence alignment of α1, α2 and α3 GlyR subunits in selected extracellular loop 2, TM2 and TM3 segments (B) Schematic depiction of wild type and point mutated α3 GlyRs. (C) Examples of current traces through wild-type and point-mutated α3 GlyRs in absence (black) or presence of NA-Gly (10 µM, red) (D) Concentration-response curves for NA-Gly in wild-type and TM2-mutated α3 GlyRs using two different glycine concentrations. Note that this specific mutation A265G in α3 GlyRs significantly attenuated the NA-Gly-induced inhibition, but did not convert the inhibition into potentiation