The Na(+)-independent Ca2+ efflux system in mitochondria is a Ca2+/2H+ exchange system

The mechanism of the Na(+)-independent Ca2+ efflux system in mitochondria has not been elucidated as yet. With the aid of cyclosporin A, an inhibitor of the Ca2(+)-induced 'pore', and using a variety of inhibitors, uncouplers and ionophores, it is possible to demonstrate, unequivocally, that this process is driven by delta pH. The efflux is not affected by delta psi, thus suggesting an electroneutral Ca2+/2H+ exchange mechanism. Parallel measurements of the rate of Ca2+ efflux and delta pH, as modulated by valinomycin and nigericin, indicate that the rate of efflux is a function of the magnitude of delta pH.