Cardiac sarcolemmal Na+-Ca2+ exchange and Na+-K+ ATPase activities and gene expression in alloxan-induced diabetes in rats |
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Authors: | Golfman Leonard Dixon Ian M.C. Takeda Nobuakira Lukas Anton Dakshinamurti Krishnamurti Dhalla Naranjan S. |
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Affiliation: | (1) Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Canada;(2) Departments of Physiology and Biochemistry, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;(3) Department of Internal Medicine, Aoto Hospital, Jikei University, Tokyo, Japan |
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Abstract: | To determine the sequence of alterations in cardiac sarcolemmal (SL) Na+-Ca2+ exchange, Na+-K+ ATPase and Ca2+-transport activities during the 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 separate group of 4 week diabetic animals were injected with insulin (3 U/day) for an additional 4 weeks. Both Na+-K+ ATPase and Ca2+-stimulated ATPase activities were depressed as early as 10 days after alloxan administration; Mg2+ ATPase activity was not depressed throughout the experimental periods. Both Na+-Ca2+ exchange and ATP-dependent Ca2+-uptake activities were depressed in diabetic hearts 2 weeks after diabetes induction. These defects in SL Na+-K+ ATPase and Ca-transport activities were normalized upon treatment of diabetic animals with insulin. Northern blot analysis was employed to compare the relative mRNA abundances of --subunit of Na+-K+ ATPase and Na+-Ca2+ exchanger in diabetic ventricular tissue vs. control samples. At 6 weeks after alloxan administration, a significant depression of the Na+-K+ ATPase -- subunit mRNA was noted in diabetic heart. A significant increase in 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 occurrence of intracellular Ca2+ overload during the development of diabetic cardiomyopathy but these defects may not be the consequence of depressed expression of genes specific for those SL proteins. |
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Keywords: | diabetic cardiomyopathy cardiac Na+-K+ ATPase cardiac Na+-Ca2+ exchange sarcolemmal Ca2+ transport sarcolemmal gene expression |
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