Cardiac sarcolemmal Na(+)-Ca2+ exchange and Na(+)-K+ ATPase activities and gene expression in alloxan-induced diabetes in rats.
To determine the sequence of alterations in cardiac sarcolemmal (SL) Na(+)-Ca2+ exchange, Na(+)-K+ ATPase and Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 alpha 1-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 alpha 1-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 Ca(2+)-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.
Golfman
L
L
St. Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Dixon
I M
IM
Takeda
N
N
Lukas
A
A
Dakshinamurti
K
K
Dhalla
N S
NS
D000496:Alloxan; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000201:enzymology* / Q000235:genetics; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D000496:Alloxan; D000254:Sodium-Potassium-Exchanging ATPase