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

To determine the role of 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 level...

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Autors principals: Wang, Y, Wilson, C, Cartwright, E, Lei, M
Format: Journal article
Publicat: Wiley 2017
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author Wang, Y
Wilson, C
Cartwright, E
Lei, M
author_facet Wang, Y
Wilson, C
Cartwright, E
Lei, M
author_sort Wang, Y
collection OXFORD
description To determine the role of 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 (PES) 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 APs of PMCA1cko atrial myocytes increased significantly under Ca2+ overload conditions and/or at higher frequency of stimulation. The decay of Na+-Ca2+ exchanger (NCX) 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.
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spelling oxford-uuid:9983948b-b940-4458-b66b-ba3536cf03f22022-03-27T00:14:53ZPlasma membrane Ca2+ ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9983948b-b940-4458-b66b-ba3536cf03f2Symplectic Elements at OxfordWiley2017Wang, YWilson, CCartwright, ELei, MTo determine the role of 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 (PES) 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 APs of PMCA1cko atrial myocytes increased significantly under Ca2+ overload conditions and/or at higher frequency of stimulation. The decay of Na+-Ca2+ exchanger (NCX) 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.
spellingShingle Wang, Y
Wilson, C
Cartwright, E
Lei, M
Plasma membrane Ca2+ ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
title Plasma membrane Ca2+ ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
title_full Plasma membrane Ca2+ ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
title_fullStr Plasma membrane Ca2+ ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
title_full_unstemmed Plasma membrane Ca2+ ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
title_short Plasma membrane Ca2+ ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
title_sort plasma membrane ca2 atpase 1 is required for maintaining atrial ca2 homeostasis and electrophysiological stability in the mouse
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AT wilsonc plasmamembraneca2atpase1isrequiredformaintainingatrialca2homeostasisandelectrophysiologicalstabilityinthemouse
AT cartwrighte plasmamembraneca2atpase1isrequiredformaintainingatrialca2homeostasisandelectrophysiologicalstabilityinthemouse
AT leim plasmamembraneca2atpase1isrequiredformaintainingatrialca2homeostasisandelectrophysiologicalstabilityinthemouse