title: Different actions of cardioprotective agents on mitochondrial Ca2+ regulation in a Ca2+ paradox-induced Ca2+ overload.
abstract: BACKGROUND
  Mitochondrial Ca2+ overload is a major cause of irreversible cell injury during various metabolic stresses. The protective effects of various agents that affect mitochondrial function against Ca2+ overload during Ca2+ paradox were investigated in rat ventricular myocytes.
  
  
  RESULTS
  On Ca2+ repletion following Ca2+ depletion, [Ca2+]i increased rapidly, and 90 of 210 cells (43%) died. In viable cells, the increase in [Ca2+]i was lower than in dead cells. KB-R7943 prevented the increase in [Ca2+]i, and completely inhibited cell death. Ruthenium red (RuR), diazoxide (Dz) or cyclosporin A (CsA) prevented cell death (15%, 26% and 17%, respectively; p < 0.05), and the protective effect of Dz was abolished by 5-hydroxydecanoate. These agents did not reduce the increase in [Ca2+]i in viable cells or the rate of initial increase in [Ca2+]i in all cells. RuR and Dz decreased [Ca2+]m in skinned myocytes, but CsA did not affect [Ca2+]m. Dz reduced NADH fluorescence, whereas RuR and CsA did not.
  
  
  CONCLUSIONS
  The protective effects of RuR and Dz could be ascribed to altered Ca2+ regulation by decreasing [Ca2+]m, and Dz could have an additional effect on oxidative phosphorylation. The protective effect of CsA could be directly associated with the mitochondrial permeability transition pore.
authors.affiliation: Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsunaga
authors.forename: Masao
authors.initials: M
authors.lastname: Saotome
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Satoh
authors.forename: Hideki
authors.initials: H
authors.lastname: Katoh
authors.forename: Hajime
authors.initials: H
authors.lastname: Terada
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014260:Triclosan
chemical_list: D002317:Cardiovascular Agents; D014260:Triclosan; D002118:Calcium