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Updated: Jun 11, 2026

Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)
Published on: August 9, 2024
LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium
Jiusheng Yan1, Richard W Aldrich
1Section of Neurobiology, Center for Learning and Memory, University of Texas, Austin, Texas 78712, USA.
Abstract:
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.
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