Calcium Handling in Inherited Cardiac Diseases: A Focus on Catecholaminergic Polymorphic Ventricular Tachycardia and Hypertrophic Cardiomyopathy

Int J Mol Sci. 2023 Feb 8;24(4):3365. doi: 10.3390/ijms24043365.

Abstract

Calcium (Ca2+) is the major mediator of cardiac contractile function. It plays a key role in regulating excitation-contraction coupling and modulating the systolic and diastolic phases. Defective handling of intracellular Ca2+ can cause different types of cardiac dysfunction. Thus, the remodeling of Ca2+ handling has been proposed to be a part of the pathological mechanism leading to electrical and structural heart diseases. Indeed, to ensure appropriate electrical cardiac conduction and contraction, Ca2+ levels are regulated by several Ca2+-related proteins. This review focuses on the genetic etiology of cardiac diseases related to calcium mishandling. We will approach the subject by focalizing on two clinical entities: catecholaminergic polymorphic ventricular tachycardia (CPVT) as a cardiac channelopathy and hypertrophic cardiomyopathy (HCM) as a primary cardiomyopathy. Further, this review will illustrate the fact that despite the genetic and allelic heterogeneity of cardiac defects, calcium-handling perturbations are the common pathophysiological mechanism. The newly identified calcium-related genes and the genetic overlap between the associated heart diseases are also discussed in this review.

Keywords: calcium mishandling; catecholaminergic polymorphic ventricular tachycardia; excitation–contraction coupling; hypertrophic cardiomyopathy.

Publication types

  • Review

MeSH terms

  • Calcium / metabolism
  • Calcium, Dietary / metabolism
  • Cardiomyopathy, Hypertrophic* / metabolism
  • Heart Diseases* / metabolism
  • Humans
  • Myocytes, Cardiac / metabolism
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Tachycardia, Ventricular* / genetics

Substances

  • Calcium
  • Calcium, Dietary
  • Ryanodine Receptor Calcium Release Channel

Supplementary concepts

  • Polymorphic catecholergic ventricular tachycardia

Grants and funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.