3 years ago

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

Wilson, Cartwright, Wang, Lei
To determine the role of 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 (PES) 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 APs 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 (NCX) 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. This article is protected by copyright. All rights reserved.

Publisher URL: http://doi.org/10.1113/JP274110

DOI: 10.1113/JP274110

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