Plasma membrane Ca2+-ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse

Abstract

Key points: The role of plasma membrane Ca2+-ATPase 1 (PMCA1) in Ca2+ homeostasis and electrical stability in atrial tissue has been investigated at both organ and cellular levels in mice with cardiomyocyte-specific deletion of PMCA1 (PMCA1cko) The PMCA1cko hearts became more susceptible to atrial arrhythmic stress conditions than PMCA1loxP/loxP hearts. PMCA1 deficiency alters cellular Ca2+ homeostasis under both baseline and stress conditions. PMCA1 is required for maintaining cellular Ca2+ homeostasis and electrical stability in murine atria under stress conditions. Abstract: To determine the role of plasma membrane Ca2+-ATPase 1 (PMCA1) in maintaining Ca2+ homeostasis and electrical stability in the atrium under physiological and stress conditions, mice with a cardiomyocyte-specific deletion of PMCA1 (PMCA1cko) and their control littermates (PMCA1loxP/loxP) were studied at the organ and cellular levels. At the organ level, the PMCA1cko hearts became more susceptible to atrial arrhythmias under rapid programmed electrical stimulation compared with the PMCA1loxP/loxP hearts, and such arrhythmic events became more severe under Ca2+ overload conditions. At the cellular level, the occurrence of irregular-type action potentials of PMCA1cko atrial myocytes increased significantly under Ca2+ overload conditions and/or at higher frequency of stimulation. The decay of Na+/Ca2+ exchanger current that followed a stimulation protocol was significantly prolonged in PMCA1cko atrial myocytes under basal conditions, with Ca2+ overload leading to even greater prolongation. In conclusion, PMCA1 is required for maintaining Ca2+ homeostasis and electrical stability in the atrium. This is particularly critical during fast removal of Ca2+ from the cytosol, which is required under stress conditions.