Na,K-ATPase receptor subunits alpha 1, alpha 2 and alpha 3 mRNA in dilated cardiomyopathy.
Na,K-ATPase receptor density has been shown to be down-regulated with decreasing ejection fraction in patients with chronic heart failure. It was the aim of the present study to determine whether down-regulation is detected also at the mRNA level. Six donor hearts and six explanted hearts due to dilated cardiomyopathy (ejection fraction 23 +/- 5%) were analyzed. RNA was extracted. Quantitative Na,K-ATPase receptor catalytic subunit alpha 1, alpha 2 and alpha 3 mRNA expression was determined by solution hybridization. No cross-reactivity occurred between the three probes. alpha 1 mRNA was expressed at about 5 and 10 times higher (p < 0.001) concentrations than alpha 2 and alpha 3 mRNA, respectively, and alpha 2 mRNA higher (p < 0.001) than alpha 3. There were no differences between right and left ventricles and between donor hearts and patients with dilated cardiomyopathy. In conclusion, Na,K-ATPase alpha 1 mRNA is the predominant subunit expressed in human myocardium. Depressed ejection fraction in dilated cardiomyopathy is not associated with changed mRNA subunit expression. Documented downregulation of Na,K-ATPase activity, therefore, may be associated with the structural and membrane-related beta subunit or posttranscriptional modification of the catalytic subunits.