Cationic amphiphiles prevent calcium leak induced by ATP depletion in myocardial cells.
Excessive calcium influx is important in the irreversible injury of cardiac myocytes and other cell types. The mechanism is unknown, but possibilities include L-type channels, Na(+)-Ca2+ exchange, sarcolemmal (SL) defects, and calcium leak channels. In this study, metabolic inhibition was used to induce ATP depletion and augmented calcium influx in cultured cardiac myocytes. Inhibition of the L-type calcium channel and Na(+)-Ca2+ exchanger had no significant effect on the calcium leak. There was no significant lactate dehydrogenase release, indicating that the leak did not occur through major SL defects. No alterations in the asymmetric distribution of SL phospholipids were demonstrated. Phospholipid rearrangements were therefore not responsible. The leak was unaffected by 0.5 mM cadmium and 1 microM nifedipine but was augmented by 50 microM nifedipine, characteristics in common with calcium leak channels. Insertion of the cationic amphiphiles dodecyltrimethylammonium bromide or polymyxin B sulfate into the SL had a profound inhibitory effect on the calcium leak. The anionic amphiphile sodium dodecyl sulfate had the opposite effect, and the neutral amphiphile lauryl acetate had no effect. These results suggest that an alteration in the SL surface charge affects calcium leak. It is proposed that the augmented calcium influx occurs via calcium leak channels and that these can be modulated by charged amphiphiles.
Clague
J R
JR
Cardiovascular Research Laboratory, UCLA School of Medicine 90024-1760.
Post
J A
JA
Langer
G A
GA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology
D015220:Calcium Channels; D000644:Quaternary Ammonium Compounds; D012967:Sodium Dodecyl Sulfate; D000255:Adenosine Triphosphate; C022806:dodecyltrimethylammonium; D011112:Polymyxin B; D002118:Calcium