Voltage-Sensing Residues in the Voltage Sensor of the BK Channel

Abstract

Voltage- and Ca2+ -activated K+ (BK) channels are modular proteins with allosteric gating. BK channels damp excitatory stimuli mediated by voltage-dependent Ca2+ channels, and they are involved in modulating physiological processes such as muscle contraction and neuronal excitability. To identify the voltage-sensing residues that contribute to the gating charge movement is crucial to understand the mechanism of BK channel voltage-dependent activation at the molecular level. Here, to determine which charged amino acids in transmembrane segments S1-S4 contribute to the voltage sensitivity of the BK channel, we have measured gating currents in BK channels containing neutralization mutations. Only neutralization of basic residues contained in S4 can decrease the voltage dependence of the BK channel voltage sensor. Neutralization of other charged residues in the voltage sensor domain changed the equilibrium of the active-resting equilibrium, revealing a modulating role in the free energy necessary to activate the voltage sensor. The results reveal that in BK channels the S4 segment is solely responsible for the gating charge movement. Supported by 1150273 to R.L. The Centro Interdisciplinario de Neurociencia de Valparaíso is a Millennium Institute (P029-022-F).