The following article requires a subscription:



(Format: HTML, PDF)

: Large-conductance, voltage- and calcium-activated potassium (BK, or KCa1.1) channels are ubiquitously expressed in electrically excitable and non-excitable cells 1,2, either as [alpha]-subunit (BK[alpha]) tetramers or together with tissue specific auxiliary [beta]-subunits ([beta]1-[beta]4) 3-5. Activation of BK channels typically requires coincident membrane depolarization and elevation in free cytosolic Ca2 concentration ([Ca2 ]i) 6,7, which are not physiological conditions for most non-excitable cells. Here we present evidence that in non-excitable LNCaP prostate cancer cells, BK channels can be activated at negative voltages without rises in [Ca2 ]i through their complex with an auxiliary protein, leucine-rich repeat (LRR)-containing protein 26 (LRRC26). 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 shift (~-140 mV) in voltage dependence and provides a molecular basis for activation of BK channels at physiological voltages and calcium levels in non-excitable cells.

(C) 2010 Nature Publishing Group