OVEREXPRESSION OF PHOSPHOLAMBAN ALTERS INACTIVATION KINETICS OF L-TYPE CA2+ CHANNEL CURRENTS IN MOUSE ATRIAL MYOCYTES

In mammalian Ventricular myocytes, inactivation of L-type Ca2+ channel s (CaCh) is controlled by voltage-and Ca2+-dependent mechanisms. The C a2+-dependent component is regulated by the Ca2+ released from the sar coplasmic reticulum (SR). However, little is known about the inactivat ion properties of CaCh in atrial myocytes, which lack spatial coupling between CaCh and SR Ca2+ release channels. The cardiac SR Ca2+ load i s determined by the activity of SR Ca2+-ATPase, which is inversely reg ulated by the levels of phospholamban (PLB). To investigate the role o f SR Ca2+ in atrial myocytes, Ca2+ currents (I-Ca) were recorded in mo use atrial myocytes recorded from wild-type (WT) mice and the characte ristics were compared to those obtained from atrial myocytes from the transgenic mice overexpressing PLB (PLB-OEX). I-Ca from WT exhibited f ast and slow components of inactivation and the rate of inactivation w as slowed when SR Ca2+ was depleted by caffeine, suggesting that the i nactivation of atrial I-Ca is modulated by SR Ca2+ load. The current d ensity and voltage-dependence of 4, were similar between the two group s. However, the fast component of inactivation was significantly reduc ed in PLB-OEX. When Ca2+ was replaced by Bali or in the presence of ca ffeine, inactivation was slowed and the decay of the current was not s ignificantly different between WT and PLB-OEX. These results suggest t hat the inactivation of I-Ca in mouse atrial myocytes involves Ca2+-de pendent and voltage-dependent components. The decrease in the faster c omponent of inactivation in PLB-OEX is consistent with the idea that C aCh and SR Ca2+ release channels are functionally coupled and Ca2+ rel eased from the SR contributes the Ca2+-dependent inactivation componen t. (C) 1998 Academic Press Limited.