New aspects in cardiac L-type Ca2+ channel regulation

Biochem Soc Trans. 2020 Feb 28;48(1):39-49. doi: 10.1042/BST20190229.

Abstract

Cardiac excitation-contraction coupling is initiated with the influx of Ca2+ ions across the plasma membrane through voltage-gated L-type calcium channels. This process is tightly regulated by modulation of the channel open probability and channel localization. Protein kinase A (PKA) is found in close association with the channel and is one of the main regulators of its function. Whether this kinase is modulating the channel open probability by phosphorylation of key residues or via alternative mechanisms is unclear. This review summarizes recent findings regarding the PKA-mediated channel modulation and will highlight recently discovered regulatory mechanisms that are independent of PKA activity and involve protein-protein interactions and channel localization.

Keywords: AKAP; Ca2+; Ca2+ channel; LTCC; PKA; compartmentalization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • A Kinase Anchor Proteins / metabolism
  • Animals
  • Binding Sites
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling / physiology*
  • Cell Membrane / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Humans
  • Myocardium / metabolism*
  • Phosphorylation
  • Protein Interaction Domains and Motifs

Substances

  • A Kinase Anchor Proteins
  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases