Advances in CaV1.1 gating: New insights into permeation and voltage-sensing mechanisms

Channels (Austin). 2023 Dec;17(1):2167569. doi: 10.1080/19336950.2023.2167569.

Abstract

The CaV1.1 voltage-gated Ca2+ channel carries L-type Ca2+ current and is the voltage-sensor for excitation-contraction (EC) coupling in skeletal muscle. Significant breakthroughs in the EC coupling field have often been close on the heels of technological advancement. In particular, CaV1.1 was the first voltage-gated Ca2+ channel to be cloned, the first ion channel to have its gating current measured and the first ion channel to have an effectively null animal model. Though these innovations have provided invaluable information regarding how CaV1.1 detects changes in membrane potential and transmits intra- and inter-molecular signals which cause opening of the channel pore and support Ca2+ release from the sarcoplasmic reticulum remain elusive. Here, we review current perspectives on this topic including the recent application of functional site-directed fluorometry.

Keywords: CaV1.1; Skeletal muscle; calcium channel; dihydropyridine receptor (DHPR); excitation-contraction (EC) coupling; functional site-directed fluorometry; voltage-clamp; voltage-sensor.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type* / genetics
  • Calcium Channels, L-Type* / metabolism
  • Excitation Contraction Coupling / physiology
  • Membrane Potentials / physiology
  • Muscle, Skeletal* / metabolism
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum / metabolism

Substances

  • Calcium Channels, L-Type
  • Calcium
  • Ryanodine Receptor Calcium Release Channel