NA,K-ATPASE RECEPTOR SUBUNITS ALPHA-1, ALPHA-2 AND ALPHA-3 MESSENGER-RNA 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. I t was the aim of the present study to determine whether down-regulatio n is detected also at the mRNA level. Six donor hearts and six explant ed hearts due to dilated cardiomyopathy (ejection fraction 23+/-5%) we re analyzed. RNA was extracted. Quantitative Na,K-ATPase receptor cata lytic subunit alpha 1, alpha 2 and alpha 3 mRNA expression was determi ned by solution hybridization. No cross-reactivity occurred between th e three probes. alpha 1 mRNA was expressed at about 5 and 10 times hig her (p<0.001) concentrations than alpha 2 and alpha 3 mRNA, respective ly, and alpha 2 mRNA higher (p<0.001) than alpha 3. There were no diff erences between right and left ventricles and between donor hearts and patients with dilated cardiomyopathy. In conclusion, Na,K-ATPase alph a 1 mRNA is the predominant subunit expressed in human myocardium. Dep ressed ejection fraction in dilated cardiomyopathy is not associated w ith 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.