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Alterations in Ca2+-channels during the development of diabetic cardiomyopathy

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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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Authors and Affiliations

  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

    Sheu Lun Lee, Ivana Ostadalova, Frantisek Kolar & Naranjan S. Dhalla

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  1. Sheu Lun Lee
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  2. Ivana Ostadalova
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  3. Frantisek Kolar
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  4. Naranjan S. Dhalla
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Lun Lee, S., Ostadalova, I., Kolar, F. et al. Alterations in Ca2+-channels during the development of diabetic cardiomyopathy. Mol Cell Biochem 109, 173–179 (1992). https://doi.org/10.1007/BF00229773

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