The Relation Between Contraction Dynamics and the Intracellular Calcium Transient in Mammalian Cardiac Muscle

Abstract

The contraction of cardiac muscle is the end result of several steps that constitute excitation-contraction coupling: action potential, entry of Ca²⁺ ions through the surface membrane, release of Ca²⁺ ions from intracellular stores (sarcoplasmic reticulum), binding of Ca²⁺ to the C subunit of the regulatory protein troponin on the thin filament, conformational changes in the thin filament to uncover the myosin binding sites on actin molecules, the binding of myosin heads of actin through the formation of myosin cross-bridges, and finally, motion of cross-bridges that result in force development and/or shortening. The detailed study of each of the above mentioned steps has become almost a field of investigation of its own. There is increasing evidence for the existence of several feedback loops between steps in excitation-contraction coupling, of which only a few will be mentioned in this chapter. Mechanical events such as changes in length alter the characteristics of both the action potential^1–4 and of the intracellular Ca²⁺ transient^4–7 detected with the Ca²⁺-regulated photoprotein aequorin8. The purpose of this brief review is to highlight the observations that changes in load or of force development influence the time course of the intracellular calcium transient in isolated cardiac muscle. It will become apparent that it is often not possible to distinguish between changes of length and of force as the primum movens for the observed changes in the intracellular calcium transient.