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.
Petrashevskaya
Natalia N
NN
Institute of Molecular Pharmacology and Biophysics, Department of Surgery, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0828, USA.
Koch
Sheryl E
SE
Bodi
Ilona
I
Schwartz
Arnold
A
D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000378:metabolism
D009569:Nitric Oxide; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D002118:Calcium