Hypersensitivity to calcium associated with an increased sarcolemmal Ca2+-ATPase activity in diabetic rat heart

Sarcolemmal Ca2+-dependent ATPase activity and the mechanical response to calcium and verapamil were studied in myocardium from normal rats and those with diabetes induced by streptozotocin. Sarcolemmal Ca2+-ATPase activity was increased in diabetic animals, depending on the duration of the diabetes. Both the maximal velocity and the affinity were greater in hearts of diabetic rats compared with normal controls. In insulin treated diabetic hearts the affinity of the enzyme for calcium decreased but the maximal velocity was not modified. The enzyme activity was stimulated maximally by millimolar concentrations of calcium and inhibited by lanthanum chloride. Calcium induced a concentration dependent increase in dF/dt in normal and diabetic hearts, but in diabetes the dose-response curve to calcium chloride was shifted to the left. Verapamil depressed the dF/dt in a concentration dependent manner in normal and diabetic hearts; but the drug was more effective in diabetic than in normal rats. These results suggest that an increase in sarcolemmal Ca2+-ATPase activity may be of critical importance in the hypersensitivity of diabetic heart in the presence of low extracellular calcium and calcium blockade.