The Ca(2+)-induced permeability transition pore is involved in Ca(2+)-induced mitochondrial oscillations. A study on...

The Ca(2+)-induced permeability transition of the mitochondrial inner membrane was studied in digitonin-permeabilized Ehrlich ascites tumour cells respiring on succinate in an isotonic medium. Addition of a sufficient amount of Ca2+ to induce an efflux of accumulated Ca2+ from mitochondria produced an oscillatory state with periodically changing rates of respiration, transmembrane potential, delta pH and direction of Ca2+ fluxes. This contrasts with liver mitochondria in which only a Ca2+ efflux is induced under these conditions. Addition of traces of cyclosporin A (approximately 0.1 nM) damped the oscillations by inhibiting the phase in which Ca2+ efflux occurs and promoting the reestablishment of a higher transmembrane potential. Efflux was also prevented by addition of ATP or ADP, ATP being more potent. Efflux was also inhibited by low concentrations of spermine. It is concluded that Ca(2+)-induced oscillations involve the cyclosporin A-sensitive pore and that the Ehrlich ascites tumour cell mitochondria differ from liver mitochondria in being far more sensitive to cyclosporin A and ATP. The possible physiological role of the oscillatory state is discussed.