The specific binding of [3H]EO-122, a radiolabeled class I antiarrhythmic drug to rat heart membranes

Abstract [ 3 H]EO-122, a radiolabeled class I antiarrhythmic drug, has been used to characterize a new specific binding system to rat heart membranes. The binding is saturable and competitive with unlabeled EO-122 and other antiarrhythmic drugs. In this system, [ 3 H]EO-122 binds to two sites. Site A with an apparent K d of 33.5 ± 1.5 n m , B max of 1.05 ± 0.15 pmol/mg protein and Hill coefficient n H = 4. Site B with an apparent K d of 233 ± 25 n m , B max equals 5.7 ± 0.61 pmol/mg proteins and n H = 6. The binding to site B indicates that this site is pharmacologically relevant to known class I A antiarrhythmic drugs such as quinidine and procainamide. Lidocaine (class I B ) does not interact with this site. Interpretation of the high Hill coefficient suggests that the binding of an antiarrhythmic drug to its pharmacologically relevant binding site exposes additional binding sites and/or modulates the affinity of adjacent binding sites.