LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium.
Large-conductance, voltage- and calcium-activated potassium (BK, or K(Ca)1.1) channels are ubiquitously expressed in electrically excitable and non-excitable cells, either as alpha-subunit (BKalpha) tetramers or together with tissue specific auxiliary beta-subunits (beta1-beta4). Activation of BK channels typically requires coincident membrane depolarization and elevation in free cytosolic Ca(2+) concentration ([Ca(2+)](i)), 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 [Ca(2+)](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 ( approximately -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.
Yan
Jiusheng
J
Section of Neurobiology, Center for Learning and Memory, University of Texas, Austin, Texas 78712, USA.
Aldrich
Richard W
RW
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000032:analysis; D045744:Cell Line, Tumor; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D051381:Rats
C539913:LRRC26 protein, human; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009363:Neoplasm Proteins; D002118:Calcium