Complex voltage-dependent behavior of single unliganded calcium-sensitive potassium channels

The study and characterization of unliganded openings is of central signifi cance for the elucidation of gating mechanisms for allosteric ligand-gated ion channels. Unliganded openings have been reported for many channel types , but their low open probability can make it difficult to study their kinet ics in detail. Because the large conductance calcium-activated potassium ch annel mSlo is sensitive to both intracellular calcium and to membrane poten tial, we have been able to obtain stable unliganded single-channel recordin gs of mSlo with relatively high opening probability. We have found that the single-channel gating behavior of mSlo is complex, with multiple open and closed states, even when no ligand is present. Our results rule out a Monod -Wyman-Changeux allosteric mechanism with a central voltage-dependent conce rted step, and they support the existence of quaternary states with less th an the full number of voltage sensors activated, as has been suggested by p revious work involving measurements of gating currents.