Modification of Vmax of canine cardiac Purkinje fibers and of the effects of lidocaine by SC-72-14.
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 Vmax 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 Vmax 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 Vmax 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.
Y
Y
Morikawa
H
H
Meiri
W
W
Spinelli
M R
MR
Rosen
R B
RB
Robinson
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008012:Lidocaine / Q000037:antagonists & inhibitors*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D000911:Antibodies, Monoclonal; D007473:Ion Channels; D008012:Lidocaine