Structure-Function Relationship of the Voltage-Gated Calcium Channel Cav1.1 Complex

Adv Exp Med Biol. 2017:981:23-39. doi: 10.1007/978-3-319-55858-5_2.

Abstract

Voltage-gated calcium (Cav) channels are miniature membrane transistors that convert membrane electrical signals to intracellular Ca2+ transients that trigger many physiological events. In mammals, there are ten subtypes of Cav channel, among which Cav1.1 is the first Cavα1 to be cloned. Cav1.1 is specified for the excitation-contraction coupling of skeletal muscles, and has been a prototype in the structural investigations of Cav channels. This article summarized the recent advances in the structural elucidation of Cav1.1 and the mechanistic insights derived from the 3.6 Å structure obtained using single-particle, electron cryomicroscopy. The structure of the Cav1.1 complex established the framework for mechanistic understanding of excitation-contraction coupling and provides the template for molecular interpretations of the functions and disease mechanisms of Cav and Nav channels.

Keywords: Cav1.1; DHPR; Structure; Voltage-gated calcium channel.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium Channels / chemistry*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / chemistry
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism
  • Cloning, Molecular
  • Cryoelectron Microscopy
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / genetics
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism
  • Mice
  • Muscle Proteins / chemistry*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal* / chemistry
  • Muscle, Skeletal* / metabolism
  • Protein Domains
  • Rats
  • Structure-Activity Relationship

Substances

  • CACNA1S protein, human
  • CACNA1S protein, mouse
  • Calcium Channels
  • Calcium Channels, L-Type
  • Kcnma1 protein, rat
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Muscle Proteins