Modulation of the mitochondrial megachannel by divalent cations and protons.
In patch-clamp experiments on rat liver mitoplasts, the 1.3 nanosiemens (in 150 mM KCl) mitochondrial megachannel was activated by Ca2+ and competitively inhibited by Mg2+, Mn2+, Ba2+, and Sr2+. Cyclosporin A, which inhibits the megachannel, also showed a competitive behavior versus Ca2+. The pore is regulated by pH in the physiological range; lower pH values cause its closure in a Ca(2+)-reversible manner. The modulating sites involved in these effects are located on the matrix side of the membrane. As illustrated in the companion paper (Bernardi, P., Vassanelli, S., Veronese, P., Colonna, R., Szabó, I., and Zoratti, M. (1992) J. Biol. Chem. 267, 2934-2939), the calcium-induced permeability transition of mitochondria is affected by these various agents in a similar manner. The results support the identification of the megachannel with the pore believed to be involved in the permeabilization process. The kinetic characteristics of the single channel events support the idea that the megachannel is composed of cooperating subunits.
Szabó
I
I
Consiglio Nazionale delle Ricerche, Centro Studi Fisiologia Mitocondri, Padova, Italy.
Bernardi
P
P
Zoratti
M
M
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent; D016572:Cyclosporine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology*; D016685:Mitomycin / Q000494:pharmacology; D051381:Rats
D002413:Cations, Divalent; D007473:Ion Channels; D001464:Barium; D016685:Mitomycin; D004533:Egtazic Acid; D016572:Cyclosporine; D008274:Magnesium; D002118:Calcium