Mechanisms and regulation of cardiac Cav1.2 trafficking

Maartje Westhoff, Rose E. Dixon

Research output: Contribution to journalReview articlepeer-review

Abstract

During cardiac excitation contraction coupling, the arrival of an action potential at the ventricular myocardium triggers voltage‐dependent L‐type Ca2+ (CaV1.2) channels in individual my-ocytes to open briefly. The level of this Ca2+ influx tunes the amplitude of Ca2+ ‐induced Ca2+ release from ryanodine receptors (RyR2) on the junctional sarcoplasmic reticulum and thus the magnitude of the elevation in intracellular Ca2+ concentration and ultimately the downstream contraction. The number and activity of functional CaV1.2 channels at the t‐tubule dyads dictates the amplitude of the Ca2+ influx. Trafficking of these channels and their auxiliary subunits to the cell surface is thus tightly controlled and regulated to ensure adequate sarcolemmal expression to sustain this critical process. To that end, recent discoveries have revealed the existence of internal reservoirs of pre-formed CaV1.2 channels that can be rapidly mobilized to enhance sarcolemmal expression in times of acute stress when hemodynamic and metabolic demand increases. In this review, we provide an overview of the current thinking on CaV1.2 channel trafficking dynamics in the heart. We highlight the numerous points of control including the biosynthetic pathway, the endosomal recycling path-way, ubiquitination, and lysosomal and proteasomal degradation pathways, and discuss the effects of β‐adrenergic and angiotensin receptor signaling cascades on this process.

Original languageEnglish (US)
Article number5927
JournalInternational journal of molecular sciences
Volume22
Issue number11
DOIs
StatePublished - Jun 1 2021

Keywords

  • Angiotensin II
  • Calcium signaling
  • Caveolae
  • Ion channel trafficking
  • L‐type calcium channels
  • T‐tubule
  • β‐adrenergic receptor

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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