Calcium cycling, historic overview and perspectives. Role for autonomic nervous system regulation

The human heart proceeds from a relaxed state (diastole) to a fully contracted state (systole) and recovery in 600ms. During this period, Ca(2+) inside the myocardial cell rises from about 10nM to about 100nM and returns to the former. The contractile-relaxation cycle is tightly coupled to the Ca(2+)transient. In the normal physiological state, the autonomic nervous system (ANS) plays a major role in the regulation of cardiac function and important changes occur in diseases of the heart. Sympathetic overdrive is a major determinant of the critical transition from initial compensatory hypertrophy to decompensated failure. Cardiac myocytes from failing hearts are characterized by a number of abnormalities in excitation-contraction coupling, that are a direct consequence of beta-adrenergic signaling defects. Although desensitized in cardiac hypertrophy and failure, the beta-adrenergic signaling pathway retains receptor capacity, a characteristic that is used in therapeutic approaches. There are several putative Ca(2+)-dependent pathways that exert counterbalancing negative regulation over cAMP-dependent positive inotropic effect and may represent potential targets for contractile stimulation. This review is focused on the interactions between sympathetic drive and aspects of calcium signaling in the heart.