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.
Sylvén
C
C
Karolinska Institute at Department of Medicine, Huddinge Hospital, Sweden.
Jansson
E
E
Sotonyi
P
P
Waagstein
F
F
Brönnegård
M
M
D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000201:enzymology*; D003429:Cross Reactions; D015342:DNA Probes; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*
D015342:DNA Probes; D007527:Isoenzymes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000254:Sodium-Potassium-Exchanging ATPase