Key result
A considerable fraction of the fluorescence signal for each CaV1.1 voltage-sensing domain occurred after the time of peak Ca2+ release, but a sizable fraction for VSDs I, II, and IV overlapped the rising phase of charge moved.
Why the study?
The mechanism linking CaV1.1 voltage sensor activation to intracellular Ca2+ release during excitation-contraction coupling was unclear, specifically whether one or all four voltage-sensing domains contribute.
This study demonstrates that the four voltage-sensing domains of CaV1.1 in skeletal muscle operate differentially during an action potential, with VSDs I, II, and IV moving faster than VSDIII.
Answers are grounded in this paper and cite their sources.
New AP fluorometry tracks individual CaV1.1 VSD movements during ECC; leaves open which domains control skeletal muscle Ca2+ release.
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.
No takes yet. Share an insight, caveat, or question.
Banks et al. (2021) studied Healthy skeletal muscle fibers (basic science). Cysteine substitutions on S4 voltage-sensing segments of CaV1.1 and AP fluorometry vs. Wild-type/untransfected muscle fibers was evaluated on Voltage sensor charge movement and fluorescence signal responses to an AP. A considerable fraction of the fluorescence signal for each CaV1.1 voltage-sensing domain occurred after the time of peak Ca2+ release, but a sizable fraction for VSDs I, II, and IV overlapped the rising phase of charge moved.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: