Decrease in Ca<SUP>2&#8290;</SUP> Storage in the Cardiac Sarcoplasmic Reticulum of Diabetic Rat

Decrease in Ca<SUP>2&#8290;</SUP> Storage in the Cardiac Sarcoplasmic Reticulum of Diabetic Rat

<P> In order to elucidate the molecular mechanism of the intracellular Ca<SUP>2&#8290;</SUP> overload frequently reported from diabetic heart, diabetic rats were induced by the administration of streptozotocin, the membrane vesicles of junctional SR (heavy SR, HSR) were isolated from the ventricular myocytes, and SR Ca<SUP>2&#8290;</SUP> uptake and SR Ca<SUP>2&#8290;</SUP> release were measured. The activity of SR Ca<SUP>2&#8290;</SUP>-ATPase was 562&#8273;14 nmol/min/mg protein in control heart. The activity was decreased to 413&#8273;30 nmol/min/mg protein in diabetic heart and it was partially recovered to 485&#8273;18 nmol/min/mg protein in insulin-treated diabetic heart. A similar pattern was observed in SR <SUP>45</SUP>Ca<SUP>2&#8290;</SUP> uptakes; the specific uptake was the highest in control heart and it was the lowest in diabetic heart. In SR <SUP>45</SUP>Ca<SUP>2&#8290;</SUP> release experiment, the highest release, 45% of SR <SUP>45</SUP>Ca<SUP>2&#8290;</SUP>, was observed in control heart. The release of diabetic heart was 20% and it was 30% in insulin-treated diabetic heart. Our results showed that the activities of both SR Ca<SUP>2&#8290;</SUP>-ATPase and SR Ca<SUP>2&#8290;</SUP> release channel were decreased in diabetic heart. In order to evaluate how these two factors contribute to SR Ca<SUP>2&#8290;</SUP> storage, the activity of SR Ca<SUP>2&#8290;</SUP>-ATPase was measured in the uncoupled leaky vesicles. The uncoupling effect which is able to increase the activity of SR Ca<SUP>2&#8290;</SUP>-ATPase was observed in control heart; however, no significant increments of SR Ca<SUP>2&#8290;</SUP>-ATPase activities were measured in both diabetic and insulin-treated diabetic rats. These results represent that the Ca<SUP>2&#8290;</SUP> storage in SR is significantly depressed and, therefore, Ca<SUP>2&#8290;</SUP>-sequestering activity of SR may be also depressed in diabetic heart.