Biochemical and structural changes in cultured heart cells induced by metabolic inhibition.
We examined the relationship between ionic homeostasis, ATP, and irreversible cell injury in cultured embryonic chick heart cells treated with rotenone (10(-4) M) alone or in combination with iodoacetate (IAA) (10(-3) M), in the presence of extracellular calcium (Ca0) (2.7 mM) and its nominal absence. Changes in Na, K, and total cell Ca content did not correlate with parameters indicative of irreversible injury, i.e., ultrastructural damage or lactate dehydrogenase (LDH) release. Because structural defects in the plasma membrane occurred without a significant release of LDH after exposure to rotenone plus IAA for 1 h, LDH release appears to be a relatively late event in cell injury. In addition, cells exposed to rotenone in the presence of Ca0 for 2.5 h showed a significant fall in ATP and a rise in LDH release. This response was attenuated in the nominal absence of Ca0, and the addition of rotenone caused an eightfold increase in intracellular sodium (Nai), whereas in the presence of Ca0, Nai increased only threefold in 2.5 h. Thus Ca0 appears to promote Nai-Ca0 exchange and lead to an increase in cell Ca that can then stimulate ATP breakdown by Ca-activated ATPases. Of the measured variables associated with myocardial cell injury, a decline in ATP correlates best with changes in either LDH or morphology. The apparent lack of correlation between changes in intracellular ion content, LDH release, and morphology supports the conclusion that myocardial cell injury is a multifactorial process.
Department of Physiology, Duke University Medical Center, Durham 27710.
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E
Murphy
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LeFurgey
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M
Lieberman
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D006019:Glycolysis / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism
D007461:Iodoacetates; D012402:Rotenone; D000255:Adenosine Triphosphate; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D011188:Potassium; D002118:Calcium; D019807:Iodoacetic Acid