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

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 (PMCA1^cko ) The PMCA1^cko hearts became more susceptible to atrial arrhythmic stress conditions than PMCA1^loxP/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 (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 Ca²⁺ overload conditions. At the cellular level, the occurrence of irregular-type action potentials of PMCA1^cko 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 PMCA1^cko 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.