Investigation of the effect of store-operated calcium channels on intercellular calcium regulation in experimental diabetic cardiomyopathy

Objective: In the diabetic cardiomyopathy model, it was aimed to investigate the role of SOCCs in the impaired intracellular Ca2+ regulation and the effects of chronic application of losartan as an angiotensin II receptor blocker on ICRAC currents and SOCE proteins. Method: H9C2 and RBL-1 cell lines were cultured in normal and high glucose environment and SOCE were examined by voltage clamping method. In rats, streptozotocin (STZ 50mg / kg) was administered intraperitoneally to create an experimental diabetes model. One week after STZ administration, DM and DM+Los group animals' blood glucose values above 300mg/dL were separated from the others. For the K+Los and DM+Los groups, losartan was administered at 30mg / kg by gavage for 4 weeks. SOCE were measured by voltage clamping method in isolated cardiomyocytes during experiment. In addition, measurement of protein expression was carried out using the western blot technique. Results: In RBL-1 and H9C2 cells grown in high glucose environment, it was observed that SOCE currents increased compared to control. It has been observed that chronically administered losartan returns this increase to control values. In adult rat cardiomyocytes, it was observed that SOC currents decreased in diabetic condition compared to control, and chronic losartan treatment returned these currents to control values. In addition, SOCE proteins were examined, it was observed that while Stim1, Stim2 and Oria2 levels did not change, the expression levels of Orai1 and Orai3 proteins were increased. Conclusion: It is thought that SOCE may play an important role in the regulation of intracellular Ca2+ regulation in cardiomyocytes, and there may be a connection between the renine-angiotensin system (RAS) and SOCE in case of diabetic cardiomyopathy. SOCE and its molecular components (STIM1/Orai1, Stim1/Orai1/TRPC) are thought to be a new therapeutic target for patients with diabetic complications. Key words: Diabetes Mellitus, SOCE, Stim, Orai