Central to controlling intracellular calcium concentration ([Ca2+]i) are a number of Ca2+ transporters and channels with the L-type Ca2+ channel, Na+-Ca2+ exchanger and sarcoplasmic reticulum Ca2+-ATPase (SERCA) being of particular note in the heart. This review concentrates on the regulation of [Ca2+]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 Ca2+ responsible for initiating contraction and relaxation in cardiac myocytes and how these can be manipulated to regulate the Ca2+ content of the major Ca2+ 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 Ca2+ in ageing and heart disease. In addition to manipulating the amplitude of the normal systolic Ca2+ transient, the tight regulation of SR Ca2+ content is also required to prevent the abnormal, spontaneous or diastolic release of Ca2+ 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 Ca2+ release channel (ryanodine receptor, RyR). How such diastolic release arises and potential mechanisms for controlling this will be discussed. © 2007 Elsevier Ltd. All rights reserved.
- Sarcoplasmic reticulum
- Sodium-calcium exchanger