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

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