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


CONCLUSIONS
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.
Xu
Kai Y
KY
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA. kxu002@umaryland.edu
Takimoto
Eiki
E
Fedarko
Neal S
NS
D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism* / Q000502:physiology
D000254:Sodium-Potassium-Exchanging ATPase