The Vertebrate Heart: Modulation of Calcium Control

Abstract

Throughout a lifetime the myocardium contracts and relaxes rhythmically and without fatigue, while constantly adapting its power output to the variable hemodynamic demands. In the beating heart, the contractile mechanism is switched on and off in a most regular manner by the rise and fall of the intracellular free calcium. To understand the control of the myocardium, therefore, we must first consider how the myoplasmic Ca²⁺ concentration is kept low in the “off-state” or diastole (Sect. 7.1), and how then the “on-state” or systole is initiated by calcium release from the sarcoplasmic reticulum and/or by a transsarcolemmal calcium influx (Sect. 7.2). The contractile machinery of the heart is never maximally stimulated so that the heart always has reserves; in fact, the calcium activator released into the myoplasm causes, at most, half-activation of the contractile proteins. Thus, there is enough “play” for up-as well as for down-regulation according to the variable demands of circulating blood. For instance, force or “contractihty” increases when more calcium is released into the myoplasm so that a higher fraction of the calcium-binding sites on the troponin molecule become occupied (Sect. 7.3). However, the decisive parameter determining contractihty is obviously not the Ca²⁺ concentration per se, but the calcium occupancy of troponin. Thus, contractihty may also be altered by changing the calcium sensitivity of the regulatory protein and, therefore, the responsiveness of the myofilaments to calcium ions (Sect. 7.4). By all of these mechanisms, the activity of the myocardium may be adapted over a wide range.