Changes in the expression of cardiac Na+-K+ ATPase subunits in the UM-X7.1 cardiomyopathic hamster
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Published on: September 24, 2013
1Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Insights
Cardiac Na+-K+ ATPase activity is reduced in cardiomyopathic hamsters. This study found altered expression of Na+-K+ ATPase subunits, suggesting a link to decreased enzyme function in heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Biochemistry
Background:
- Cardiac Na+-K+ ATPase activity is crucial for maintaining heart function.
- Previous studies indicate reduced Na+-K+ ATPase activity in UM-X7.1 hamsters with genetic cardiomyopathy.
- The underlying mechanisms for this activity decrease remain unclear.
Purpose of the Study:
- To investigate if altered expression of cardiac Na+-K+ ATPase subunits correlates with reduced enzyme activity in UM-X7.1 cardiomyopathic hamsters.
- To compare protein and mRNA levels of Na+-K+ ATPase subunits between affected hamsters and controls.
Main Methods:
- Examined sarcolemmal Na+-K+ ATPase activity in hearts of 250-day-old UM-X7.1 and control Syrian hamsters.
- Utilized Western blot analysis to quantify protein expression of alpha1, alpha2, alpha3, and beta1 subunits.
- Employed Northern blot analysis to assess mRNA levels of the same subunits.
Main Results:
- Na+-K+ ATPase activity was significantly lower in UM-X7.1 hearts compared to controls.
- Protein content of alpha1 and beta1 subunits increased, while alpha2 and alpha3 subunits decreased in UM-X7.1 hearts.
- mRNA levels mirrored protein changes, with elevated alpha1 and beta1, and reduced alpha2 subunit expression.
Conclusions:
- Changes in the expression of Na+-K+ ATPase subunits are associated with the depressed enzyme activity observed in UM-X7.1 cardiomyopathic hearts.
- Altered subunit expression may be a key factor contributing to the reduced cardiac Na+-K+ ATPase function in this genetic model of cardiomyopathy.
Abstract:
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.
