Altered pyruvate dehydrogenase control and mitochondrial free Ca2+ in hearts of cardiomyopathic hamsters
| Autor: | I Kudryashova, CZ Fan, F Di Lisa, Giovanni Gambassi, Barbara A. Hogue, Richard G. Hansford |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Systole Physiology Hamster Pyruvate Dehydrogenase Complex Stimulation Dehydrogenase Cell Separation Oxidative phosphorylation Mitochondrion Biology Tricarboxylate Mitochondria Heart Diastole Cricetinae Physiology (medical) Internal medicine medicine Animals Myocyte Ketoglutarate Dehydrogenase Complex Myocardium Osmolar Concentration Settore MED/09 - MEDICINA INTERNA Pyruvate dehydrogenase complex Myocardial Contraction Endocrinology Calcium Cardiomyopathies Cardiology and Cardiovascular Medicine |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 264:H2188-H2197 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.1993.264.6.h2188 |
| Popis: | The fraction of total pyruvate dehydrogenase in the active, dephosphorylated form is much lower in the glucose-perfused isolated hearts of two myopathic strains of Syrian hamster (BIO 14.6 and TO-2) than in the hearts of healthy control animals (F1B). The myopathic hearts also develop significantly less pressure under these conditions. Experiments with isolated myocytes from the BIO 14.6 heart reveal that intramitochondrial free Ca2+ ([Ca2+]m), a positive effector of pyruvate dehydrogenase interconversion, rises much less in response to a protocol of increased frequency of electrical stimulation and adrenergic stimulation than does [Ca2+]m in cells from the healthy control animals (viz from 248 +/- 15 to 348 +/- 44 nM in BIO 14.6 vs. from 241 +/- 35 to 830 +/- 124 nM in F1B, at 4 Hz). As the concentration of Ca2+ that produces half-maximal activation of pyruvate dehydrogenase within mitochondria is 650 nM, this difference between strains is likely the mechanism of the altered enzyme interconversion. The lesser response of [Ca2+]m to electrical stimulation in the BIO 14.6 cells probably results mainly from smaller systolic transients in cytosolic free Ca2+ in response to excitation of single myocytes from the BIO 14.6 animal. Lowered values of [Ca2+]m within the range described would compromise not only pyruvate dehydrogenase activity, but also flux through the tricarboxylate cycle in the myopathic heart, owing to the sensitivity of 2-oxoglutarate dehydrogenase to Ca2+. This may explain the decreased activity of oxidative phosphorylation and performance of work in the myopathic heart. |
| Databáze: | OpenAIRE |
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