Defective activity and isoform of the Na,K-ATPase in the dilated cardiomyopathic hamster
F Paganelli1, R Mougenot, J M Maixentt
1Department of Cardiology, H pital Nord, Marseille, France.
Insights
Dilated cardiomyopathy in hamsters shows reduced sodium-potassium adenosine triphosphatase (Na,K-ATPase) activity and specific isoform changes, mirroring findings in human heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Sodium-potassium adenosine triphosphatase (Na,K-ATPase) is crucial for cardiac function.
- Its impairment is observed in human heart failure with dilation.
- Limited information exists regarding Na,K-ATPase in animal models of idiopathic dilated cardiomyopathy.
Purpose of the Study:
- To investigate Na,K-ATPase isoform composition and activity in a hamster model of dilated cardiomyopathy.
- To compare these findings with healthy controls.
Main Methods:
- Studied cardiomyopathic MS 200 hamsters and healthy Syrian hamsters.
- Utilized isoform-specific antibodies to analyze Na,K-ATPase alpha and beta1 subunits in ventricular myocardium.
- Quantified Na,K-ATPase activity in homogenate and membrane fractions.
Main Results:
- Dilated cardiomyopathy in hamsters showed significantly reduced membrane alpha1 and beta1 isoform abundances.
- Na,K-ATPase activity was reduced by 35% compared to healthy controls (p<0.05).
- No significant changes were observed in the Na,K-ATPase alpha2-subunit.
Conclusions:
- Dilated cardiomyopathy in this hamster model specifically reduces membrane alpha1 and beta1 isoform abundance.
- This reduction correlates with decreased Na,K-ATPase activity, similar to human dilated heart failure.
- Provides a relevant animal model for studying Na,K-ATPase dysfunction in heart failure.
Abstract:
The Na,K-ATPase function appears impaired in human heart failure with dilation; however little is known in animal model with idiopathic dilated cardiomyopathy. We studied Na,K-ATPase isoform composition and activity from cardiomyopathic hamsters of the MS 200 strain with pure dilated cardiomyopathy and compared them with those of healthy Syrian hamsters. 150-day-old male MS 200 Syrian hamsters (n = 16) and sex- and age-matched healthy Syrian hamsters (n = 15) were used. Antibodies specific for the three alpha-isoforms and against the beta1-isoform were used to study Na,K-ATPase isoform expression in ventricular myocardium. Na,K-ATPase activity was quantified in homogenate and membrane fractions. There was no significant change in left ventricular mass. Morphological examination revealed a decreased septum thickness in the dilated cardiomyopathy compared with control hamster. Idiopathic dilated cardiomyopathy in hamsters presented significantly reduced membrane alpha1 and beta1 abundances and reduced Na,K-ATPase activity (-35% vs. healthy control, p<0.05). Chronic heart failure had no effect on the Na,K-ATPase alpha2-subunit protein. We have demonstrated for the first time that dilated cardiomyopathy induces a specific reduction of both membrane alpha1- and beta1-isoform abundance and Na,K-ATPase activity in hamsters similar to those previously reported in human dilated heart failure.
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