The pathogenesis of free radical-induced calcium leak in cultured rat cardiomyocytes.
Elevated levels of intracellular calcium are generally accepted to be of critical importance in determining the outcome of cardiac myocytes exposed to ischemia and reperfusion. The mechanisms involved are obscure, but a favorite candidate is the Na-Ca exchanger operating in reversed mode, permitting calcium influx. Using exogenous free radicals and a unique, on-line, isotopic technique to measure calcium fluxes in cultured neonatal rat cardiomyocytes, we show that Na-Ca exchange is not the primary mechanism of calcium overload in this cell type during free radical exposure. We also demonstrate that neither L-type calcium channels nor general sarcolemmal defects are responsible. A specific calcium leak is present at a time when the sarcolemma remains intact with respect to its potassium permeability. The leak shares many properties with specific calcium leak channels demonstrated electrophysiologically in other tissues. It can be modulated by alterations in surface charge such that cationic amphiphiles inhibit the leak and anionic amphiphiles augment it. It is concluded that the calcium leak, in this cell type, is specific to calcium and that leak channels may be responsible.
Clague
J R
JR
Cardiovascular Research Laboratory, UCLA School of Medicine 90024-1760.
Langer
G A
GA
D000818:Animals; D017920:Antiporters / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D005609:Free Radicals; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011197:Potassium Radioisotopes; D051381:Rats; D012964:Sodium; D019831:Sodium-Calcium Exchanger
D017920:Antiporters; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D005609:Free Radicals; D010743:Phospholipids; D011197:Potassium Radioisotopes; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D002118:Calcium