RGD Reference Report - Evidence that the H1-H2 domain of alpha1 subunit of (Na++K+)-ATPase participates in the regulation of cardiac contraction. - Rat Genome Database

Send us a Message



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

Evidence that the H1-H2 domain of alpha1 subunit of (Na++K+)-ATPase participates in the regulation of cardiac contraction.

Authors: Xu, KY  Takimoto, E  Juang, GJ  Zhang, Q  Rohde, H  Myers, AC 
Citation: Xu KY, etal., FASEB J. 2005 Jan;19(1):53-61.
RGD ID: 6903236
Pubmed: PMID:15629895   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.04-2329com   (Journal Full-text)

(Na++K+)-ATPase (NKA) plays an important role in ion homeostasis and regulates cardiac contraction. To understand the molecular basis of its cardiac regulatory functions, we investigated whether the primary structure of the H1-H2 domain in alpha-1 (alpha1) subunit of the enzyme plays a role in myocardial contractile regulation. Here we show that site-specific binding to this 1 H1-H2 domain with a targeted antibody (SSA78) markedly augments intracellular Ca2+ transients and contraction of rat ventricular cardiomyocytes without inactivating NKA. In vivo SSA78 infusion in mice results in a positive inotropic effect with enhanced contractile function yet no change in relaxation, indicating a direct cardiac effect linked to the H1-H2 domain. Competitive immunofluorescent staining and flow cytometry reveal that SSA78 binding is antagonized by ouabain, supporting the interaction of SSA78 at one of the glycoside-effecter sites. These new findings suggest that the H1-H2 domain of 1 subunit of NKA is a critical determinant of enzyme biologic activity, which couples to enhanced myocyte calcium transient and inotropic action.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of cardiac muscle cell contraction  IMP 6903236 RGD 

Objects Annotated

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


Additional Information