Binding of bepridil to isolated rat heart mitochondria

We investigated mass action of isolated rat heart mitochondria with the calcium antagonist bepridil. At pH 7.20 bepridil in basic form b associates rapidly with the mitochondrial membrane but the amount fixed is higher in non-energized mitochondria than in mitochondria energized by succinate or ATP Mg2+. This effect is related to the dissociation state of the drug since conditions favoring the acidic form bH+ suppress this difference. Tritiated bepridil bound to mitochondrial membrane is only partially displaced by high concentrations of unlabeled drug (greater than or equal to 510(-5) M). No membrane energization effect is noted on this displacement. Binding values of bepridil to mitochondrial membrane (KD 1.710(-5) M; Bmax 23.8 nmol.mg-1 protein) show only low affinity receptor sites. Bepridil binding to the lipid part of the inner membrane surface is postulated. This interaction is used to explain some of the in vitro effects of this calcium antagonist on membrane bound enzyme activities.