Activation of (Na+ + K+)-ATPase induces positive inotropy in intact mouse heart in vivo

Kai Y. Xu, Eiki Takimoto, Neal S. Fedarko

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: We have recently identified an activation site on (Na+ + K+)-ATPase and found that binding of antibody SSA412 to this specific site of the enzyme markedly augments (Na+ + K+)-ATPase catalytic activity. Demonstration of whether activation of (Na+ + K+)-ATPase affects heart function in animal in vivo was the object of this investigation. Methods: Male wild-type CD-1 mouse and specific antibody SSA412 were used for the study. A pressure-volume micromanometer-conductance catheter in anesthetized mouse assessed in vivo cardiac functions. Results: Specific antibody SSA412 infusion in mouse shifted pressure-volume loop leftward with increased stroke volume and enhanced end-systolic elastance. Global systolic parameters such as ejection fraction and cardiac output, and load independent contractile parameters including dP/dtmax/IP, PMX/EDV, Ees, and PRSW, were all increased without any effect on relaxation following administration of SSA412. Cardiac preload indexed by EDV and afterload by ESP did not alter, suggesting that SSA412-enhanced myocardial performance is a direct cardiac effect caused by the activation of (Na+ + K+)-ATPase. Conclusion: Our study provides the first in vivo physiological evidence to demonstrate that activation of (Na+ + K+)-ATPase induces significant positive inotropic effect in intact animal heart. The finding may lead to new therapeutic strategies for the treatment of heart failure.

Original languageEnglish (US)
Pages (from-to)582-587
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number2
DOIs
StatePublished - Oct 20 2006

Keywords

  • (Na + K)-ATPase (Na/K-pump)
  • Contractile function
  • Inotropic agent
  • Myocytes
  • Sarcolemma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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