DECREASED NA,K-ATPASE GENE-EXPRESSION IN CARDIOMYOPATHIC HAMSTER HEARTS

We studied Na,K-ATPase mRNA expression in cardiomyopathic (Bio 14.6) a nd normal (F1b) Syrian hamster ventricles. In Northern blot analysis, Na,K-ATPase alpha1, alpha2, alpha3 and beta1 isoform mRNAs were detect ed in 3-week-old Bio 14.6 and F1b hamster ventricles. We then investig ated the expression of alpha1 subunit mRNA in Bio 14.6 hamster ventric les at the ages of 3 weeks prehypertrophic and 30 weeks hypertrophic, and in age-matched F1b hamster ventricles. The alpha1 subunit mRNA lev els in Bio 14.6 hamster ventricles were approximately 50% lower than t hose in F1b hamster ventricles at both 3 and 30 weeks of age. Na,K-ATP ase activity measured in membrane fractions from the ventricles of 3-w eek-old Bio 14.6 hamsters was also approximately 20% lower than that o f F1b hamsters, suggesting that the differences in the mRNA level were associated with the differences in the protein level. We conclude tha t Na,K-ATPase mRNA expression and enzyme activity are significantly de creased in the hearts of Bio 14.6 hamsters even before the onset of hy pertrophy and cardiomyopathy, suggesting that the altered expression o f Na,K-ATPase gene is an early event in the pathogenesis of cardiomyop athy in this animal model.