Internal pH, Na+, and Ca2+ regulation by trimetazidine during cardiac cell acidosis.
The effects of trimetazidine were studied on plasma membrane structures of cardiac cells which control excitability, as well as on cardiac cells that were cultured in normal physiologic conditions and after intracellular acidification. When cardiac cells were kept in normal physiologic conditions, trimetazidine at concentrations ranging from 10(-8) to 3.10(-4) M interacted neither directly nor indirectly with the major ionic transporter systems of cardiac cells, such as ionic channels (Na+, K+), ATPase, Na+/H+, and Na+/Ca2+ exchange systems. Under acid-load conditions trimetazide acts in a dose- and time-dependent manner, in limiting the accumulation of Na+ and Ca2+ inside cardiac cells and depressing intracellular cell acidosis. It is proposed that trimetazidine plays a key role in limiting the intracellular accumulation of protons that is responsible for cell acidosis during ischemia. Trimetazidine, in protecting cardiac cells against accumulation of protons, limits accumulation of Na+ and Ca2+.
Renaud
J F
JF
Centre de Biochimie du CNRS, Faculté des Sciences, Nice, France.
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D006863:Hydrogen-Ion Concentration; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D014292:Trimetazidine / Q000494:pharmacology*
D012964:Sodium; D014292:Trimetazidine; D002118:Calcium