Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPase
Cytosolic Na + concentrations regulate cardiac excitation-contraction coupling and contractility. Inhibition of the Na+/K+-ATPase (NKA) activity increases cardiac contractility by increasing cytosolic Ca2+ levels, as increased cytosolic Na+ levels are coupled to less Ca2+ extrusion and/or increased...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.827334/full |
| _version_ | 1811235881255698432 |
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| author | Jonas Skogestad Jonas Skogestad Jan Magnus Aronsen Jan Magnus Aronsen |
| author_facet | Jonas Skogestad Jonas Skogestad Jan Magnus Aronsen Jan Magnus Aronsen |
| author_sort | Jonas Skogestad |
| collection | DOAJ |
| description | Cytosolic Na + concentrations regulate cardiac excitation-contraction coupling and contractility. Inhibition of the Na+/K+-ATPase (NKA) activity increases cardiac contractility by increasing cytosolic Ca2+ levels, as increased cytosolic Na+ levels are coupled to less Ca2+ extrusion and/or increased Ca2+ influx from the Na+/Ca2+-exchanger. NKA consists of one α subunit and one β subunit, with α1 and α2 being the main α isoforms in cardiomyocytes. Substantial evidence suggests that NKAα2 is the primary regulator of cardiac contractility despite being outnumbered by NKAα1 in cardiomyocytes. This review will mainly focus on differential regulation and subcellular localization of the NKAα1 and NKAα2 isoforms, and their relation to the proposed concept of subcellular gradients of Na+ in cardiomyocytes. We will also discuss the potential roles of NKAα2 in mediating cardiac hypertrophy and ventricular arrhythmias. |
| first_indexed | 2024-04-12T11:59:43Z |
| format | Article |
| id | doaj.art-ecc47e8e836646d3b885c423c77e23a3 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T11:59:43Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ecc47e8e836646d3b885c423c77e23a32022-12-22T03:33:53ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-06-011310.3389/fphys.2022.827334827334Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPaseJonas Skogestad0Jonas Skogestad1Jan Magnus Aronsen2Jan Magnus Aronsen3Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Pharmacology, Oslo University Hospital, Oslo, NorwayDepartment of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Pharmacology, Oslo University Hospital, Oslo, NorwayCytosolic Na + concentrations regulate cardiac excitation-contraction coupling and contractility. Inhibition of the Na+/K+-ATPase (NKA) activity increases cardiac contractility by increasing cytosolic Ca2+ levels, as increased cytosolic Na+ levels are coupled to less Ca2+ extrusion and/or increased Ca2+ influx from the Na+/Ca2+-exchanger. NKA consists of one α subunit and one β subunit, with α1 and α2 being the main α isoforms in cardiomyocytes. Substantial evidence suggests that NKAα2 is the primary regulator of cardiac contractility despite being outnumbered by NKAα1 in cardiomyocytes. This review will mainly focus on differential regulation and subcellular localization of the NKAα1 and NKAα2 isoforms, and their relation to the proposed concept of subcellular gradients of Na+ in cardiomyocytes. We will also discuss the potential roles of NKAα2 in mediating cardiac hypertrophy and ventricular arrhythmias.https://www.frontiersin.org/articles/10.3389/fphys.2022.827334/fullNKAsodiumcalciumion gradientsNCXCardiomyocyte |
| spellingShingle | Jonas Skogestad Jonas Skogestad Jan Magnus Aronsen Jan Magnus Aronsen Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPase Frontiers in Physiology NKA sodium calcium ion gradients NCX Cardiomyocyte |
| title | Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPase |
| title_full | Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPase |
| title_fullStr | Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPase |
| title_full_unstemmed | Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPase |
| title_short | Regulation of Cardiac Contractility by the Alpha 2 Subunit of the Na+/K+-ATPase |
| title_sort | regulation of cardiac contractility by the alpha 2 subunit of the na k atpase |
| topic | NKA sodium calcium ion gradients NCX Cardiomyocyte |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.827334/full |
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