Calcium Cycling, Historic Overview and Perspectives. Role for Autonomic Nervous System Regulation

N. N. Petrashevskaya, S. E. Koch, I. Bodi and A. Schwartz. Calcium Cycling, Historic Overview and Perspectives. Role for Autonomic Nervous System Regulation. Journal of Molecular and Cellular Cardiology (2002)34 , 885–896. The human heart proceeds from a relaxed state (diastole) to a fully contracted state (systole) and recovery in 600 ms. During this period, Ca2+ inside the myocardial cell rises from about 10 nM to about 100 nM and returns to the former. The contractile-relaxation cycle is tightly coupled to the Ca2+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 β-adrenergic signaling defects. Although desensitized in cardiac hypertrophy and failure, the β-adrenergic signaling pathway retains receptor capacity, a characteristic that is used in therapeutic approaches. There are several putative Ca2+-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.