The determinants of contractility in the heart.
The contraction-relaxation cycle of the heart represents the combined action of a variety of different components of the myocytes. For many years an 'index' of contractility has been sought as a means of describing and integrating the large amount of information available from the studies of heart muscle contraction. This review will undertake to show that dF/dt, recorded from the whole heart, and dT/dt, recorded in isometric studies of isolated heart muscle preparations, should not be considered as the 'index' of contractility. Examples will be presented in which an increasing dT/dt is paradoxically accompanied by a lower tension, while a decreasing dT/dt can occur concomitantly with an increased contractile tension. Arguments are further presented in support of the concept that Ca2+, in conjunction with troponin C, is the main determinant of cardiac contractility and that dT/dt reflects a dynamic equilibrium between free and troponin-bound Ca2+. Peak tension is thus the net result of overlapping events competing for Ca2+ during the latter part of contraction, that is, during Phase II of contraction as defined below. These suggestions are based upon the following considerations: (a) The Ca2+ pumps are active even during rest and serve to maintain low cytosolic Ca2+ levels. (b) As cytosolic Ca2+ concentration increases, Ca2+ pump activity also increases. (c) In addition, the Na+/Ca2+ exchange is activated by elevated Ca2+ concentrations and serves to decrease cytosolic Ca2+ levels. (d) The net result is a decline in free Ca2+ concentration during Phase II and a reduction in the rate of cross-bridge formation until peak tension is reached. Thus, the Ca2+ handling elements of the myocyte serve as a finely tuned feedback device, regulating troponin C-Ca2+ interactions controlling the Ca2+ concentration of the cytosol and as a result, the actin and myosin interaction. Factors which influence the function of these elements will change the contractility of the heart.
Penefsky
Z J
ZJ
Department of Pharmacology, State University of New York, Syracuse 13210.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*
D002316:Cardiotonic Agents; D002118:Calcium