Alterations in Ca2+-channels during the development of diabetic cardiomyopathy |
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Authors: | Sheu Lun Lee Ivana Ostadalova Frantisek Kolar Naranjan S Dhalla |
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Institution: | (1) Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Department of Physiology Faculty of Medicine, University of Manitoba Winnipeg, R2H 2A6 Manitoba, Canada;(2) Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, R2H 2A6 Winnipeg, Manitoba, Canada |
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Abstract: | In order to examine the status of Ca2+ channels in heart sarcolemma during the development of diabetes, rats were injected intravenously with 65 mg/kg streptozotocin and hearts were removed 1, 3 and 8 weeks later. Crude membranes from the ventricular muscle were prepared and the specific binding of 3H-nitrendipine was studied by employing different concentrations of this Ca 2+-antagonist. A significant decrease in both dissociation constant and maximal number of 3H-nitrendipine binding was observed in 3 and 8 weeks diabetic preparations. No such alterations were evident in diabetic brain membranes. Treatment of diabetic animals with insulin prevented the occurrence of these changes in the myocardium. The altered 3H-nitrendipine binding characteristics in diabetic heart membranes may not be due to the high levels of circulating catecholamines in this experimental model because no such changes were seen upon injecting a high dose (40 mg/kg) of isoproterenol in rats for 24 hr. The reduced number of 3H-nitrendipine binding sites may decrease Ca2+-influx through voltage sensitive Ca2+ channels and partly explain the depressed cardiac contractile force development in chronic diabetes whereas the increased affinity of Ca2+ channels may partly explain the increased sensitivity of diabetic heart to Ca 2+. |
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Keywords: | sarcolemmal Ca 2+ channels nitrendipine binding Ca2+-antagonists diabetes-induced heart dysfunction |
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