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Alterations in Ca(2+)-channels during the development of diabetic cardiomyopathy
S L Lee1, I Ostadalova, F Kolar
1Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Manitoba, Canada.
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 Ca(2+)-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 Ca2+.
Insights
Diabetes alters calcium (Ca2+) channels in heart sarcolemma, reducing their number and increasing affinity. Insulin treatment prevents these changes, impacting cardiac function in diabetic rats.
Area of Science:
- Cardiovascular Physiology
- Diabetology
- Pharmacology
Background:
- Diabetes mellitus is associated with cardiac dysfunction.
- Alterations in sarcolemmal calcium channels may contribute to diabetic cardiomyopathy.
- Understanding Ca2+ channel status is crucial for managing diabetic heart disease.
Purpose of the Study:
- To investigate changes in Ca2+ channels in rat heart sarcolemma during diabetes development.
- To determine the effect of insulin treatment on these Ca2+ channels.
- To explore the mechanisms underlying Ca2+ channel alterations in diabetic hearts.
Main Methods:
- Induction of diabetes in rats using streptozotocin.
- Preparation of crude membranes from ventricular muscle.
- Assessment of 3H-nitrendipine binding to Ca2+ channels at various time points (1, 3, 8 weeks).
- Evaluation of isoproterenol effects on Ca2+ channels.
- Assessment of insulin's protective effects.
Main Results:
- Significant decrease in dissociation constant and maximal binding of 3H-nitrendipine in diabetic heart membranes at 3 and 8 weeks.
- No alterations observed in diabetic brain membranes.
- Insulin treatment prevented these changes in the myocardium.
- High-dose isoproterenol did not induce similar changes, suggesting catecholamines are not the primary cause.
Conclusions:
- Diabetes leads to significant alterations in cardiac sarcolemmal Ca2+ channels, characterized by reduced binding sites and increased affinity.
- These changes may contribute to depressed cardiac contractility and altered Ca2+ sensitivity in chronic diabetes.
- Insulin therapy can prevent these detrimental effects on cardiac Ca2+ channels.