Modulation of cardiac contractility by myosin light chain phosphorylation

MOORE, R. L., T. I. MUSCH, and J. Y. CHEUNG. Modulation of cardiac contractility by myosin light chain phosphorylation. Med. Sci. Sports Exerc., Vol. 23, No. 10, pp. 1163–1169, 1991. Cytosolic free [Ca2+] ([Ca2+]e) mediates primary regulation of cardiac contractility. Both the magnitude and timecourse of [Ca2+]e transient that is elicited by a sarcolemmal action potential play central roles in defining the characteristics of the mechanical response that occurs during a single excitation-contraction coupling cycle. Numerous modulators of cardiac contractility, both hormonal and autoregulatory, act to influence contractile function via direct effects on various cellular processes that govern [Ca2+]e dynamics. Cardiac contractility can also be influenced by mechanisms that alter the responsiveness of the contractile element to activation by Ca2+ (see preceding paper). There is growing interest in the possibility that the phosphorylation of the P-light chain subunit of cardiac myosin by a Ca2+-calmodulin-dependent myosin light chain kinase may modulate cardiac muscle contractility by increasing the sensitivity of the contractile element to activation by Ca2+. The types of experimental data that have led to the development of this hypothesis and the unique aspects of cardiac P-light chain phosphate content regulation will be briefly addressed in this paper. Furthermore, several unresolved issues regarding the functional significance of cardiac P-light chain phosphorylation in intact myocardium are identified.