Overexpression of phospholamban alters inactivation kinetics of L-type Ca2+ channel currents in mouse atrial myocytes

• Published in: Journal of molecular and cellular cardiology 1998-02, Vol.30 (2), p.317-325
• Main Authors: Masaki, H, Sako, H, Kadambi, V J, Sato, Y, Kranias, E G, Yatani, A
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channels - metabolism; Calcium Channels, L-Type; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Gene Expression; Heart Atria - cytology; Heart Atria - metabolism; In Vitro Techniques; Kinetics; Membrane Potentials; Mice; Mice, Transgenic; Myocardium - cytology; Myocardium - metabolism; Patch-Clamp Techniques; Sarcoplasmic Reticulum - metabolism
• ISSN: 0022-2828
• DOI: 10.1006/jmcc.1997.0594

In mammalian ventricular myocytes, inactivation of L-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 (I Ca) 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). ICa from 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 atrial ICa is modulated by SR Ca2+ load. The current density and voltage-dependence of ICa were 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 of ICa in 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.