Changes in the expression of cardiac Na+-K+ ATPase subunits in the UM-X7.1 cardiomyopathic hamster.
Previous studies have shown that cardiac Na+ -K+ ATPase activity in the UM-X7.1 hamster strain is decreased at an early stage of genetic cardiomyopathy and remains depressed; however, the mechanism for this decrease is unknown. The objective of the present study was to assess whether changes in the expression of cardiac Na+-K+ ATPase subunits in control and UM-X7.1 cardiomyopathic hamsters are associated with alterations in the enzyme activity. Accordingly, we examined sarcolemmal Na+-K+ ATPase activity as well as protein content and mRNA levels for the alpha1, alpha2, alpha3 and beta1-subunit of the Na+-K+ ATPase in 250-day-old UM-X7.1 and age-matched, control Syrian hamsters; this age corresponds to the severe stage of heart failure in the UM-X7.1 hamster. Na+-K+ ATPase activity in UM-X7.1 hearts was decreased compared to controls (9.0 +/- 0.8 versus 5.6 +/- 0.8 micromol Pi/mg protein/hr). Western blot analysis revealed that the protein content of Na+-K+ ATPase alpha1- and beta1-subunits were increased to 164 +/- 27% and 146 +/- 22% in UM-X7.1 hearts respectively, whereas that of the alpha2- and alpha3-subunits were decreased to 82 +/- 5% and 69 +/- 11% of control values. The results of Northern blot analysis for mRNA levels were consistent with the protein levels; mRNA levels for the alpha1- and beta1-subunits in UM-X7.1 hearts were elevated to 165 +/- 14% and 151 +/- 10%, but the alpha2-subunit was decreased to 60 +/- 8% of the control value. We were unable to detect mRNA for the alpha3-subunit in either UM-X7. 1 or control hearts. These data suggest that the marked depression of Na+-K+ ATPase activity in UM-X7.1 cardiomyopathic hearts may be due to changes in the expression of subunits for this enzyme.
Kato
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Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Lukas
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A
Chapman
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Dhalla
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D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000235:genetics; D006224:Cricetinae; D046911:Macromolecular Substances; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D012508:Sarcolemma / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000378:metabolism
D046911:Macromolecular Substances; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase