The role of calcium in the response of cardiac muscle to stretch

This review focuses on the complex interactions between two major regulator s of cardiac function; Ca2+ and stretch. Initial consideration is given to the effect of stretch on myocardial contractility and details the rapid and slow increases in contractility. These are shown to be related to two dive rse changes in Ca2+ handling (enhanced myofilament Ca2+ sensitivity and inc reased intracellular Ca2+ Ca2+ is also demonstrated with respect to the tra nsient, respectively). Interaction between stretch and Ca2+ rhythm of cardi ac contraction. Stretch has been shown to alter action potential configurat ion, generate stretch-activated arrhythmias, and increase the rate of beati ng of the sino-atrial node. A variety of Ca2+-dependent mechanisms includin g attenuation of Ca2+ extrusion via Na+/Ca2+ exchange, Ca2+ entry through s tretch-activated channels (SACs) and mobilisation of intracellular Ca2+ sto res have been proposed to account for the effect of stretch on rhythm. Fina lly, the interaction between stretch and Ca2+ in the secretion of natriuret ic peptides and onset of hypertrophy is discussed. Evidence is presented th at Ca2+ (entering through L-type Ca2+ channels or SACs, or released from sa rcoplasmic reticular stores) influences secretion of both atrial and B-type natriuretic peptide; there is data to support both positive and negative m odulation by Ca2+. Ca2+ also appears to be important in the pathway that le ads to expression of precursors of hypertrophic protein synthesis. In concl usion, two of the major regulators of cardiac muscle function, Ca2+ and str etch, interact to produce effects on the heart; in general these effects ap pear to be additive. (C) 1998 Elsevier Science Ltd. All rights reserved.