Leucine Rich Repeat Containing Protein 26 (LRRC26)

Large-conductance, voltage- and calcium-activated potassium (BK) channels are ubiquitously expressed in electrically excitable and non-excitable cells, either as alpha-subunit tetramers or together with tissue specific auxiliary beta-subunits. Activation of BK channels typically requires coincident membrane depolarization and elevation in free cytosolic Ca(2+) concentration, which are not physiological conditions for most non-excitable cells. LRRC26 modulates the gating of a BK channel by enhancing the allosteric coupling between voltage-sensor activation and the channel's closed-open transition. This finding reveals a novel auxiliary protein of a voltage-gated ion channel that gives an unprecedentedly large negative shiftin voltage dependence and provides a molecular basis for activation of BK channels at physiological voltages and calcium levels in non-excitable cells.