Plasma membrane Ca(2+)‐ATPase 1 is required for maintaining atrial Ca(2+) homeostasis and electrophysiological stability in the mouse

KEY POINTS: The role of plasma membrane Ca(2+)‐ATPase 1 (PMCA1) in Ca(2+) homeostasis and electrical stability in atrial tissue has been investigated at both organ and cellular levels in mice with cardiomyocyte‐specific deletion of PMCA1 (PMCA1(cko)). The PMCA1(cko) hearts became more susceptible to atrial arrhythmic stress conditions than PMCA1(loxP/loxP) hearts. PMCA1 deficiency alters cellular Ca(2+) homeostasis under both baseline and stress conditions. PMCA1 is required for maintaining cellular Ca(2+) homeostasis and electrical stability in murine atria under stress conditions. ABSTRACT: To determine the role of plasma membrane Ca(2+)‐ATPase 1 (PMCA1) in maintaining Ca(2+) homeostasis and electrical stability in the atrium under physiological and stress conditions, mice with a cardiomyocyte‐specific deletion of PMCA1 (PMCA1(cko)) and their control littermates (PMCA1(loxP/loxP)) were studied at the organ and cellular levels. At the organ level, the PMCA1(cko) hearts became more susceptible to atrial arrhythmias under rapid programmed electrical stimulation compared with the PMCA1(loxP/loxP) hearts, and such arrhythmic events became more severe under Ca(2+) overload conditions. At the cellular level, the occurrence of irregular‐type action potentials of PMCA1(cko) atrial myocytes increased significantly under Ca(2+) overload conditions and/or at higher frequency of stimulation. The decay of Na(+)/Ca(2+) exchanger current that followed a stimulation protocol was significantly prolonged in PMCA1(cko) atrial myocytes under basal conditions, with Ca(2+) overload leading to even greater prolongation. In conclusion, PMCA1 is required for maintaining Ca(2+) homeostasis and electrical stability in the atrium. This is particularly critical during fast removal of Ca(2+) from the cytosol, which is required under stress conditions.