MELATONIN PREVENTS THE SUPPRESSION OF CARDIAC CA2+-STIMULATED ATPASE ACTIVITY-INDUCED BY ALLOXAN

The effects of melatonin treatment on cardiac sarcolemmal membrane function were investigated in alloxan-injected rats. Ca2+-stimulated adenosinetriphosphatase (ATPase, Ca2+ pump) and Mg2+-ATPase activities were depressed significantly in sarcolemmal preparations from alloxan-injected rats compared with levels in control rats. These deficits were observed 2 days after alloxan injection, and they were accompanied by an increase in the density of voltage-sensitive calcium channels, as measured by the [H-3]nitrendipine-binding assay. In a dose-dependent manner, treatment of rats with melatonin before alloxan injection significantly overcame the suppression of Ca2+-stimulated ATPase in cardiac sarcolemma. Melatonin (1, 5, and 10 mg/kg) overcame Ca2+-stimulated ATPase suppression by 13, 35, and 70%, respectively. In addition, melatonin at a dose of 10 mg/kg also prevented the suppression of the Mg2+-ATPase by 31%. The number of [H-3]nitrendipine-binding sites was not influenced by melatonin. The patent Na+-K+-ATPase and ouabain-sensitive Na+-K+-ATPase activities were not different between the control and experimental groups. The results indicate that Ca2+ pump activity is suppressed by acute alloxan treatment, whereas the density of voltage-sensitive calcium channels is increased. These changes may be a consequence of alloxan toxicity to the cardiac sarcolemma. Melatonin, likely because of its antioxidant capacity, exerts a protective effect on heart sarcolemmal membrane function in alloxan-injected rats.