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In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in a selective reduction of myocardial alpha 3 isoform of Na, K-ATPase activity. The aim of this study was to evaluate if a similar change in the two canine digitalis receptor isoforms occurs following 4 weeks of rapid ventricular pacing-induced heart failure without profound necrosis. Heart failure was induced in dogs by rapid ventricular pacing (240 beats x min-1). Digitalis receptors were quantitated by [3H]-ouabain binding with isolated microsomal membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by Western blot analysis using specific alpha 1 and alpha 3 polyclonal antibodies. In kinetic studies, similar dissociation rates of 19 to 22 x 10(-4) s-1 and 1.3 to 2.4 x 10(-4) s-1 corresponding to high and low affinity sites respectively, were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance of alpha 1 isoform in the two groups; however, levels of alpha 3 were increased by at least 50% in pacing-induced heart failure animals. In conclusion, heart failure selectively modulates the expression of cardiac alpha 3 isoform in dogs.
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