Using the lipid-reconstitution system, we could now investigate the possibility that changes in lipid membrane dynamics could affect GIRK2 function20, 21. We tested the effect of compounds demonstrated previously to increase membrane elasticity, e.g., β-octyl glucoside (β-OG) and capsaicin41, 42. Direct application of β-OG (1 mM) or capsaicin (30 μM) did not alter the rate of K+ flux for GIRK2 channels reconstituted into liposomes with brain PIP2 (Fig. 3e). There was no significant change in the rate of K+ flux with increasing concentrations of β-OG or capsaicin, in contrast to the change in K+ flux with ethanol (Fig. 3f). Taken together, these experiments demonstrate that known lipid-membrane disruptors have little effect on GIRK2 channel activity, providing additional support for the direct activation of GIRK2 by ethanol.
