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The Na+/K+-ATPase alpha2-isoform regulates cardiac contractility in rat cardiomyocytes.

Authors: Swift, F  Tovsrud, N  Enger, UH  Sjaastad, I  Sejersted, OM 
Citation: Swift F, etal., Cardiovasc Res. 2007 Jul 1;75(1):109-17. Epub 2007 Mar 24.
Pubmed: (View Article at PubMed) PMID:17442282
DOI: Full-text: DOI:10.1016/j.cardiores.2007.03.017

OBJECTIVE: The presence of both alpha1- and alpha2-isoforms of the Na+/K+-ATPase (NKA) in cardiomyocytes indicates different functions. We hypothesized that preferential localization of the alpha2-isoform to the t-tubules, locally controlling the Na+/Ca2+-exchanger (NCX), underlies a specific role in Ca2+ handling. METHODS: We studied NKA isoform distribution in isolated cardiomyocytes from Wistar rats using immunocytochemistry. NKA pump and NCX currents (I(pump) and I(NCX)) were measured in control and detubulated cardiomyocytes. Intracellular Na+ concentration [Na+]i was assessed with the fluorescent dye SBFI. RESULTS: The alpha2-isoform abundance was higher in the t-tubules than in the surface sarcolemma. We established that 0.3 microM ouabain specifically blocked the alpha2-isoform in isolated rat cardiomyocytes. This low concentration blocked 10.7+/-0.6% of I(pump) in control, but only 6.0+/-0.5% in detubulated cardiomyocytes. Moreover, measured and calculated alpha1-specific and alpha2-specific I(pump) in control (547+/-29 pA and 66 pA, respectively) and in detubulated cells (495+/-30 pA and 31 pA, respectively) showed that 53% of the alpha2-isoform, but only 9.5% of the alpha1-isoform, were localized to the t-tubules. Despite the small abundance of the alpha2-isoform (approximately 11% of total NKA), selective inhibition of this isoform induced a 40% increase in contractility in field stimulated cardiomyocytes, but no increase in global [Na+]i. However, inhibition of the alpha2-isoform increased I(NCX) indicating local subsarcolemmal accumulation of Na+ near NCX. CONCLUSIONS: The alpha2-isoform of the NKA is functionally coupled to the NCX and can regulate Ca2+ handling without changing global [Na+]i.

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CRRD Object Information
CRRD ID: 6903343
Created: 2012-10-02
Species: All species
Last Modified: 2012-10-02
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.