Small alcohols destabilize the KcsA tetramer via their effect on the membrane lateral pressure.

Previously, it was shown that the tetrameric potassium channel KcsA when present in a lipid bilayer can be dissociated by trifluoroethanol [van den Brink-van der Laan, E., et al. (2004) Biochemistry 43, 4240-4250]. Here, we demonstrate that this is a general property of small alcohols. We found that small alcohols dissociate the KcsA tetramer, at a concentration that depends on their membrane affinity. Importantly, the efficiency of the alcohol-induced tetramer dissociation was found to correlate with the efficiency of both alcohol-induced bilayer leakage and acyl chain disordering. Our data suggest that the ability of small alcohols to induce KcsA tetramer dissociation and to function as anesthetics depends on their effect on the membrane lateral pressure.