Increase of ATP-sensitive potassium (KATP) channels in the heart of type-1 diabetic rats

Background: An impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days to 3 months of induction. ATP sensitive potassium (K-ATP) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac K-ATP channels in diabetic disorders. Methods: Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on cardiac function and the expression of K-ATP channels. K-ATP channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of K-ATP channels by Western blot and Northern blot analysis. Results: The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of K-ATP channel. Two subunits of cardiac K-ATP channel (SUR2A and kir 6.2) were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac K-ATP in these diabetic rats. Conclusions: Both mRNA and protein expression of cardiac K-ATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some K-ATP channel drugs.