THE CA2-INDUCED PERMEABILITY TRANSITION PORE IS INVOLVED IN CA2+-INDUCED MITOCHONDRIAL OSCILLATIONS - A STUDY ON PERMEABILIZED EHRLICH ASCITES TUMOR-CELLS()

The Ca2+-induced permeability transition of the mitochondrial inner me mbrane was studied in digitonin-permeabilized Ehrlich ascites tumour c ells respiring on succinate in an isotonic medium. Addition of a suffi cient amount of Ca2+ to induce an efflux of accumulated Ca2+ from mito chondria produced an oscillatory state with periodically changing rate s of respiration, transmembrane potential, Delta pH and direction of C a2+ fluxes. This contrasts with liver mitochondria in which only a Ca2 + efflux is induced under these conditions. Addition of traces of cycl osporin A (approximately 0.1 nM) damped oscillations by inhibiting the phase in which Ca2+ efflux occurs and promoting the reestablishment o f a higher transmembrane potential. Efflux was also prevented by addit ion of ATP or ADP, ATP being more potent. Efflux was also inhibited by low concentrations of spermine. It is concluded that Ca2+-induced osc illations involve the cyclosporin A-sensitive pore and that the Ehrlic h ascites tumour cell mitochondria differ from liver mitochondria in b eing far more sensitive to cyclosporin A and ATP. The possible physiol ogical role of the oscillatory state is discussed.