Do stretch-induced changes in intracellular calcium modify the electrical activity of cardiac muscle?

Stretch of the myocardium influences the shape and amplitude of the intracellular Ca2+ ([Ca2+](i)) transient. Under isometric conditions stretch immediately increases myofilament Ca2+ sensitivity, increasing force production and abbreviating the time course of the [Ca2+](i) transient (the rapid response). Conversely, muscle shortening can prolong the Ca2+ transient by decreasing myofilament Ca2+ sensitivity. During the cardiac cycle, increased ventricular dilation may increase myofilament Ca2+ sensitivity during diastolic filling and the isovolumic phase of systole, but enhance the decrease in myofilament Ca2+ sensitivity during the systolic shortening of the ejection phase. If stretch is maintained there is a gradual increase in the amplitude of the Ca2+ transient and force production, which takes several minutes to develop fully (the slow response). The rapid and slow responses have been reported in whole hearts and single myocytes. Here we review stretch-induced changes in [Ca2+](i) and the underlying mechanisms. Myocardial stretch also modifies electrical activity and the opening of stretch-activated channels (SACs) is often used to explain this effect. However, the myocardium has many ionic currents that are regulated by [Ca2+](i) and in this review we discuss how stretch-induced changes in [Ca2+](i) can influence electrical activity via the modulation of these Ca2+-dependent currents. Our recent work in single ventricular myocytes has shown that axial stretch prolongs the action potential. This effect is sensitive to either SAC blockade, by streptomycin or the buffering of [Ca2+](i) with BAPTA, suggesting that both SACs and [Ca2+](i) are important for the full effects of axial stretch on electrical activity to develop. (C) 2003 Elsevier Science Ltd. All rights reserved.