CARDIAC SARCOLEMMAL NA-CA2+ EXCHANGE AND NA+-K+ ATPASE ACTIVITIES ANDGENE-EXPRESSION IN ALLOXAN-INDUCED DIABETES IN RATS()

To determine the sequence of alterations in cardiac sarcolemmal (SL) N a+-Ca2+ exchange, Na+-K+ ATPase and Ca2+-transport activities during t he development of diabetes, rats were made diabetic by an intravenous injection of 65 mg/kg alloxan. SL membranes were prepared from control and experimental hearts 1-12 weeks after induction of diabetes. A sep arate group of 4 week diabetic animals were injected with insulin (3 U /day) for an additional 4 weeks. Both Na+-K+ ATPase and Ca2+-stimulate d ATPase activities were depressed as early as 10 days after alloxan a dministration; Mg2+ ATPase activity was not depressed throughout the e xperimental periods. Both Na+-Ca2+ exchange and ATPdependent Ca2+-upta ke activities were depressed in diabetic hearts 2 weeks after diabetes induction. These defects in SL Na+-K+ ATPase and Ca-transport activit ies were normalized upon treatment of diabetic animals with insulin. N orthern blot analysis was employed to compare the relative mRNA abunda nces of alpha(1)-subunit of Na+-K+ ATPase and Na+-Ca2+ exchanger in di abetic ventricular tissue vs, control samples. At 6 weeks after alloxa n administration, a significant depression of the Na+-K+ ATPase alpha( 1)- subunit mRNA was noted in diabetic heart. A significant increase i n the Na+-Ca2+ exchanger mRNA abundance was observed at 3 weeks which returned to control by 5 weeks. The results from the alloxan-rat model of diabetes support the view that SL membrane abnormalities in Na+-K ATPase, Na+Ca2+ exchange and Ca2+-pump activities may lead to the occ urrence of intracellular Ca2+ overload during the development of diabe tic cardiomyopathy but these defects may not be the consequence of dep ressed expression of genes specific for those SL proteins.