We study the fundamental properties of heart cells and the impact of intracellular signaling mechanisms on the regulation of contractility. During excitation-contraction (EC) coupling in cardiac myocytes the influx of Ca2+ ions carried by the Ca2+ current (ICa) activates a large release of Ca2+ from intracellular stores in the sarcoplasmic reticulum (SR) via the SR Ca2+ release channel. The subsequent declining phase of this [Ca2+]i transient is due, in part, to Ca2+ reuptake mediated by the SR Ca2+ pump. Thus this movement of Ca2+ ions is a central feature of heart cell function. Recently we have studied how the hormone angiotensin II increases contractility by regulating Ca2+ currents, various protein kinases and phospholipases in intact cardiac cells. We have also recently discovered a crucial role of dephosphorylation in controlling EC coupling. Thus we use a novel integrated strategy of biochemistry, gene transfection, single cell voltage clamp, and high resolution confocal Ca2+ imaging to define important molecular regulatory mechanisms in heart.
duBell,W.H., Gaa,S.T., Lederer,W.J., and Rogers, T.B. (1998) Independent Inhibition of Calcineurin and K+ Currents by the Immunosupressant FK-506 in Rat Ventricle Am. J. Physiol., 275, H2041-H2052