Alterations of sarcolemmal Na+-Ca2+ exchange in catecholamine-induced cardiomyopathy.
Rats were injected intraperitoneally with 40 mg/kg body weight isoproterenol and the heart sarcolemma was isolated 3, 9 and 24 hours later. The heart/body weight ratio increased and varying degrees of change in cardiac ultrastructure were apparent at 9 and 24 hours after isoproterenol injection. Na+-dependent Ca2+ uptake activities of heart sarcolemma were depressed at 3, 9 and 24 hours; such alterations in 24 hour preparations were evident at different times of incubation and at different concentrations of Ca2+. No differences in Na+-induced Ca2+ release or Na+-K+ ATPase activities were observed between the control and experimental membranes. The control and isoproterenol-treated heart sarcolemmal preparations were minimally but equally contaminated by other subcellular organelles. Although there was no significant change in the phospholipid composition, the protein pattern as determined by gel electrophoresis was altered in sarcolemma at 24 hours of isoproterenol treatment. These results indicate an abnormality of heart sarcolemmal Na+-dependent Ca+ uptake during the development of catecholamine-induced cardiotoxicity. It is suggested that a depression in the ability of the cell to remove Ca2+ through the Na+-Ca2+ exchange in sarcolemma may contribute to the development of intracellular Ca2+ overload in catecholamine induced cardiomyopathy.
Makino
N
N
Dhruvarajan
R
R
Elimban
V
V
Beamish
R E
RE
Dhalla
N S
NS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002306:Cardiac Volume / Q000187:drug effects; D002312:Cardiomyopathy, Hypertrophic / Q000139:chemically induced* / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D007473:Ion Channels / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000187:drug effects* / Q000648:ultrastructure; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D007473:Ion Channels; D008563:Membrane Lipids; D008565:Membrane Proteins; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D002118:Calcium