Progressive decay of Ca(2+) homeostasis in the development of diabetic cardiomyopathy

BACKGROUND: Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca(2+) homeostasis. This study investigated the effects of alterations in Ca(2+) homeostasis and sarcoplasmic reticulum Ca(2+)-associated proteins on cardiac function in the development of diabetic cardiomyopathy. METHODS: Sprague–Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca(2+) spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca(2+)-associated proteins were assessed by Western blotting. RESULTS: Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca(2+) spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca(2+) spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca(2+)-2ATPase (SERCA) and Na(+)/Ca(2+) exchanger (NCX1) were decreased, together with quantitative alterations in Ca(2+)regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats. CONCLUSIONS: Ca(2+) sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca(2+)-associated proteins.