Analysis of cellular calcium fluxes in cardiac muscle to understand calcium homeostasis in the heart

Cell Calcium. Oct-Nov 2007;42(4-5):503-12. doi: 10.1016/j.ceca.2007.04.002. Epub 2007 May 16.

Abstract

Central to controlling intracellular calcium concentration ([Ca(2+)](i)) are a number of Ca(2+) transporters and channels with the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) being of particular note in the heart. This review concentrates on the regulation of [Ca(2+)](i) in cardiac muscle and the homeostatic mechanisms employed to ensure that the heart can operate under steady-state conditions on a beat by beat basis. To this end we discuss the relative importance of various sources and sinks of Ca(2+) responsible for initiating contraction and relaxation in cardiac myocytes and how these can be manipulated to regulate the Ca(2+) content of the major Ca(2+) store, the sarcoplasmic reticulum (SR). We will present a simple feedback system detailing how such control can be achieved and highlight how small perturbations to the steady-state operation of the feedback loop can be both beneficial physiologically and underlie changes in systolic Ca(2+) in ageing and heart disease. In addition to manipulating the amplitude of the normal systolic Ca(2+) transient, the tight regulation of SR Ca(2+) content is also required to prevent the abnormal, spontaneous or diastolic release of Ca(2+) from the SR. Such diastolic events are a major factor contributing to the genesis of cardiac arrhythmias in disease situations and in recently identified familial mutations in the SR Ca(2+) release channel (ryanodine receptor, RyR). How such diastolic release arises and potential mechanisms for controlling this will be discussed.

Publication types

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

MeSH terms

  • Aging
  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / metabolism
  • Calcium / metabolism*
  • Calcium Channels, L-Type / physiology
  • Heart Diseases / metabolism
  • Homeostasis
  • Humans
  • Ion Transport
  • Myocardial Contraction*
  • Myocardium / metabolism*
  • Sarcoplasmic Reticulum / metabolism
  • Sodium-Calcium Exchanger / physiology

Substances

  • Calcium Channels, L-Type
  • Sodium-Calcium Exchanger
  • Calcium