ON THE INTERACTIONS OF CA2-A WITH A MITOCHONDRIAL INNER MEMBRANE PORE- A STUDY USING COBALTAMMINE COMPLEX INHIBITORS OF THE CA2+ UNIPORTER( AND CYCLOSPORINE)

The mitochondrial inner membrane contains a Ca2+-activated pore possib le relevance to the pathogenesis of ischaemia/ reperfusion injury whic h is inhibited the immunosuppressant cyclosporin A (CSA). The present study employs a number of novel cobaltammine inhibitors of the Ca2+ un iporter (mediating Ca2+ uptake) to examine whether intramitochondrial Ca2+ influences the capacity of CSA to block the pore. Using dissipati on the inner membrane as means of monitoring the state of pore, it is shown that CSA blockade is facilitated as Ca2+ uptake is restricted. C a2+ also depresses and reverses the binding of [H-3]CSA to mitochondri a, but Ca2+ is ineffective when its uptake is prevented. It is conclud ed that a high intramitochondrial Ca2+ concentration antagonizes pore inhibition by CSA. The significance of this is discussed.