ABSTRACT
Cardiac excitation-contraction (E-C) coupling refers to the cascade of biological processes that begins with the cardiac action potential and ends with myocyte contraction and relaxation. It is intimately related to calcium homeostasis, myofilament sensitivity, and functions of cytoskeletal and sarcomeric proteins. E-C coupling forms the biophysical underpinnings of the inotropic state of the heart and accordingly, plays a central role in the pathogenesis and treatment of heart failure. In addition, physiological processes in the intact heart associated with E-C coupling (e.g. force-frequency relations, post-extrasystolic potentiation) are important because they (1) are fundamental physiological control mechanisms; (2) are frequently utilized as indices of myocardial function; and (3) play a role in the response to exercise.1-3
The investigation of E-C coupling highlights the advantages and limitations of a parochial approach to scientific study (i.e. reductionist cellular versus integrative physiological). Thus, whereas E-C coupling involves specific subcellular movements of calcium ions, its ultimate impact on cardiac performance results from a complex interplay between the intrinsic properties of the cardio-myocytes, chamber properties, loading conditions, and the extracellular matrix. Moreover, in vitro studies are critically dependent on experimental conditions; for example, the sarcoplasmic reticulum (SR) Ca2+ load is sensitive to many experimental variables, including frequency, temperature, mean [Ca2+]i, [Na+]i, [K+]i, action potential configuration and duration. Thus clear insight into the physiology of E-C coupling requires complementary studies at the isolated myocyte and intact organism levels. Nevertheless, since E-C coupling in health and disease are, by first principles, manifestations of myocyte calcium handling, a firm grasp of the calcium transient and calcium homeostasis is warranted.
