Voltage sensor movements of Ca _V 1.1 during an action potential in skeletal muscle fibers

Abstract

Significance A continuously evolving question regarding excitation–contraction coupling (ECC) in skeletal muscle has been around the mechanism that links the activation of the Ca V 1.1 voltage sensor with the intracellular Ca 2+ release. Ca V 1.1 senses changes in transmembranal voltage through four distinct voltage-sensing domains (VSDs I–IV), yet whether one or all contribute to ECC is unknown. To investigate the roles of each VSD, this work introduces AP fluorometry to track conformational changes of Ca V 1.1 voltage sensors and AP voltage clamp to measure the charge movement during an AP waveform in muscle fibers. The rising phase of the fluorescence signals from VSDs I, II, and IV were faster than that of VSDIII, suggesting a differential contribution of VSD movements to ECC.