Modification of Vmax of Canine Cardiac Pur kin je Fibers and of the Effects of Lidocaine by SC-72-14

SUMMARY. We used standard microelectrode techniques to determine the effects of SC-72-14, a monoclonal antibody to the fast sodium channel, on the transmembrane potentials and Vm,, of canine cardiac Purkinje fibers, and to study the interactions of the monoclonal antibody with lidocaine. SC-72-14 was prepared with receptor-rich membrane fragments of homogenized eel electroplax as the antigen. It reduced V,, ^ in a concentration-dependent fashion, and depressed membrane responsiveness, as well. These effects were attributable specifically to SC-72-14, and not to other substances in the vehicle. At slow rates of stimulation, the actions of SC-72-14 and lidocaine on V ^ equaled the sum of their effects, administered alone. These results are consistent with the interpretation that SC-72-14 and the local anesthetic did not compete for the same binding site. In contrast, at fast stimulation rates, the use-dependent blocking effects of lidocaine were suppressed by SC-72-14. The basis for the interference with the use-dependent action of lidocaine is not readily apparent, but may be the result of SC-72-14-induced changes in channel state, receptor affinity for drug, or the availability of ionized drug molecules. These possibilities all await further testing. (Circ Res 57: 354-361 1985) IN STUDIES of the fast sodium channels of excitable tissues, drugs or toxins usually are used to modify the fast inward current (e.g., Kao, 1966; Narahashi, 1974; Cahalan, 1980; Catterall, 1980; Sigworth and Neher, 1980). The effects of these agents on the transmembrane potential and the action potential upstroke appear to result from their binding to a particular site or sites in the channel, resulting in modulation of Na+ entry. Lidocaine, which de-creases the fast inward current in nerve, skeleta