RGD Reference Report - The Na+/K+-ATPase alpha2-isoform regulates cardiac contractility in rat cardiomyocytes. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

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.
RGD ID: 6903343
Pubmed: PMID:17442282   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cardiores.2007.03.017   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
intercalated disc located_inIDA 6903343; 6903343PMID:17442282BHF-UCL 
sarcolemma located_inIDA 6903343PMID:17442282BHF-UCL 
sarcolemma  IDA 6903343 RGD 
T-tubule located_inIDA 6903343; 6903343PMID:17442282BHF-UCL 
T-tubule  IDA 6903343 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
steroid hormone binding enablesIDA 6903343PMID:17442282BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Atp1a1  (ATPase Na+/K+ transporting subunit alpha 1)
Atp1a2  (ATPase Na+/K+ transporting subunit alpha 2)

Additional Information