Overexpression of Phospholamban Alters Inactivation Kinetics of -type Ca2+Channel Currents in Mouse Atrial Myocytes

In mammalian ventricular myocytes, inactivation of -type Ca2+channels (CaCh) is controlled by voltage- and Ca2+-dependent mechanisms. The Ca2+-dependent component is regulated by the Ca2+released from the sarcoplasmic reticulum (SR). However, little is known about the inactivation properties of CaCh in atrial myocytes, which lack spatial coupling between CaCh and SR Ca2+release channels. The cardiac SR Ca2+load is determined by the activity of SR Ca2+-ATPase, which is inversely regulated by the levels of phospholamban (PLB). To investigate the role of SR Ca2+in atrial myocytes, Ca2+currents (ICa) were recorded in mouse atrial myocytes recorded from wild-type (WT) mice and the characteristics were compared to those obtained from atrial myocytes from the transgenic mice overexpressing PLB (PLB-OEX).ICafrom WT exhibited fast and slow components of inactivation and the rate of inactivation was slowed when SR Ca2+was depleted by caffeine, suggesting that the inactivation of atrialICais modulated by SR Ca2+load. The current density and voltage-dependence ofICawere similar between the two groups. However, the fast component of inactivation was significantly reduced in PLB-OEX. When Ca2+was replaced by Ba2+or in the presence of caffeine, inactivation was slowed and the decay of the current was not significantly different between WT and PLB-OEX. These results suggest that the inactivation ofICain mouse atrial myocytes involves Ca2+-dependent and voltage-dependent components. The decrease in the faster component of inactivation in PLB-OEX is consistent with the idea that CaCh and SR Ca2+release channels are functionally coupled and Ca2+released from the SR contributes the Ca2+-dependent inactivation component.