Calcium waves: physiological relevance in cardiac function.

Abstract

Modulation of the cytosolic Ca2+ concentration ([Ca2+]i) constitutes a fundamental mechanism of signal transduction in excitable cells. Generally, this phenomenon is triggered by an excitation process of the external membrane and subsequently leads to activation of functional proteins specific to the cell type in which the increase of [Ca2+]i has occurred. However, in addition to the normal excitation-activation coupling providing Ca2+ influx, fluctuations in [Ca2+]i can occur spontaneously, without external electrical or hormonal stimulation. A spontaneous increase in Ca2+concentration can occur at a single focus or multiple foci within a cell and can lead to propagation of an elevation of [Ca2+]i throughout the cytosol in a wave-like pattern. Although these Ca2+ waves have been observed widely in both excitable and inexcitable cells,1 their role in the cardiac cell function remains unclear. In the last 2 decades, a substantial body of literature documenting Ca2+ waves in cardiac tissues has been created. Studies on waves in cardiac cells provided fundamental information about the role of the sarcoplasmic reticulum (SR) in excitation-contraction coupling.2 Local contractions were reported in cells with disrupted sarcolemma,2 clearly demonstrating that Ca2+ waves were not related to depolarization of the membrane. Interest in cardiac Ca2+ waves was further stimulated by a study that suggested a role for them in the generation of abnormal, nondriven electrical activity of the heart.3 Initially, Ca2+ waves in cardiac muscle were assessed indirectly from observations of local sarcomere contraction and waves of propagating sarcomere shortening,4 5 and direct evidence of spontaneous fluctuations in [Ca2+]i was obtained from analysis of aequorin photoluminescence.6 7 Progress in the development of digital-imaging techniques and fluorescent Ca2+-sensitive …