Key result
hSlo1 RKK mutants with β1 or β4 subunits increase gate opening and negatively shift voltage ~200 mV.
Why the study?
Auxiliary beta subunits and the intracellular RKK segment of human Slo1 both regulate BK channel intrinsic gate open probability, but how they function together to control the gate remained unclear.
Population
Large-conductance Ca2+- and voltage-gated K+ channel complexes
Comparison
Inclusion of beta1 or beta4 with select RKK segment mutations vs wild-type conditions
Design
In vitro electrophysiological, double-mutant cycle, and molecular modelling study
Authors
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Findings remain preclinical; extends molecular understanding of BK channel gating but leaves therapeutic translation open.
Electrostatic interactions between the Slo1 RKK segment and β N-terminal segments are critical determinants of the intrinsic open probability of the BK channel ion conduction gate.
Tian et al. (2021) studied BK channel gating. Mutations in hSlo1 RKK segment and coassembly with β1/β4 subunits vs. Wild-type hSlo1 channels was evaluated on Voltage dependence of activation (V0.5) and intrinsic open probability (L0). Coassembly of hSlo1 RKK-segment mutants with β1 or β4 subunits dramatically increases intrinsic gate opening probability and shifts voltage dependence to the negative direction by up to 200 mV.
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