Related Experiment Videos
Creatine kinase and mechanical and mitochondrial functions in hereditary and diabetic cardiomyopathies
V I Veksler1, I Murat, R Ventura-Clapier
1Laboratoire de physiologie cellulaire cardiaque, INSERM U-241, Université Paris-Sud, Orsay, France.
Insights
Cardiomyopathies alter heart muscle function and mitochondrial creatine kinase (CK) activity. This study investigated CK function in diabetic rats and hereditary cardiomyopathy hamsters, revealing impaired mitochondrial CK in both models.
Area of Science:
- Biochemistry
- Cardiology
- Molecular Biology
Background:
- Cardiomyopathies are diseases of the heart muscle.
- Creatine kinase (CK) plays a vital role in cellular energy metabolism, particularly in the heart.
- Alterations in CK function may contribute to cardiomyopathies.
Purpose of the Study:
- To investigate the functional properties of cardiac contractile apparatus and mitochondria in cardiomyopathies.
- To determine if creatine kinase (CK) function is altered in two distinct cardiomyopathy models.
Main Methods:
- Utilized ventricular skinned fibers from Syrian hamsters with hereditary dilated cardiomyopathy and diabetic rats.
- Assessed maximal calcium-activated tension and calcium sensitivity of myofibrillar proteins.
- Evaluated mitochondrial function, including respiration and oxidative phosphorylation, using saponin-skinned fibers.
Main Results:
- Hereditary cardiomyopathic fibers showed decreased maximal tension; diabetic fibers had increased calcium sensitivity.
- Myofibrillar CK was unchanged in both models.
- Mitochondrial creatine kinase (CK) activity was significantly depressed in both hereditary and diabetic cardiomyopathies, indicated by reduced creatine-stimulated respiration.
Conclusions:
- Mitochondrial creatine kinase (CK) function is impaired in both hereditary dilated cardiomyopathy and diabetic cardiomyopathy.
- These findings suggest that mitochondrial CK dysfunction contributes to the pathogenesis of cardiomyopathies.
Abstract:
To determine whether the development of cardiomyopathies is associated with alterations in creatine kinase function, the functional properties of cardiac contractile apparatus and mitochondria were studied in two different models of cardiomyopathies, the Syrian hamster (hereditary dilated cardiomyopathy, strain UM-X7.1, 200 days old) and the diabetic rat (4-6 weeks after injection of streptozotocin) using ventricular skinned fibers. After Triton X-100 treatment, the hereditary cardiomyopathic fibers demonstrated decreased maximal calcium-activated tension and unchanged calcium sensitivity, whereas fibers from diabetic hearts exhibited unchanged maximal tension and increased calcium sensitivity, when compared with their respective controls. In both cases myofibrillar creatine kinase appeared unchanged. The functional properties of total tissue mitochondria were evaluated using saponin-skinned fibers. Coupling between oxidation and phosphorylation was not altered in cardiomyopathies. Respiration rate (per unit of tissue dry weight) was normal in hereditary cardiomyopathy but was considerably lower in diabetic fibers compared with control fibers. In both models of cardiomyopathies, creatine-stimulated respiration was significantly lower than in controls, thus indicating the depression of functional activity of mitochondrial creatine kinase.