Mechanisms of Action of Lidocaine and Quinidine on Action Potential Duration in Rabbit Cardiac Purkinje Fibers

The effects of lidocaine and quinidine on rabbit cardiac Purkinje fibers were compared at 37 °C, using action potential and voltage clamp measurements. At therapeutic concentrations (5 /ig/ml), lidocaine shortened the duration of the action potential while quinidine lengthened it. When membrane potential was held constant between —40 and —50 mV by the application of the two-microelectrode voltage clamp, holding current consistently became more outward with lidocaine (+2.3 ± 0.7 nA, mean ± SEM, n = 5), but it either did not change or became more inward with quinidine (-2.1 ± 1.4 nA, n = 5). Both drugs reduced the outward tails generally associated with deactivation of the delayed rectifier current, ix. The depression of delayed rectification by quinidine (—68 ± 6%, n = 5) was greater than that produced by lidocaine (—12 ± 4%, n = 5), and can explain the observed prolongation of the action potential. To evaluate the possibility that lidocaine blocks steady state sodium channels, experiments were performed with tetrodotoxin (TTX), a specific blocker of sodium channels in a variety of excitable membranes. TTX at concentrations of 0.1-5 /tM shortened the action potential, reducing its duration to 50% of control at 1.6 JIM. Voltage clamp experiments revealed a small TTX-sensitive component of steady state current flowing at membrane potentials positive to —80 mV. In the presence of 10 /IM TTX, lidocaine failed to produce additional steady outward membrane current. These data suggest that (1) lidocaine and quinidine differ substantially in their modification of membrane channels, with quinidine having a strong effect on delayed rectification, (2) a TTX-sensitive "window" current exists in the rabbit Purkinje fiber and helps maintain the action potential plateau, and (3) the effect of lidocaine on the cardiac action potential results primarily from block of TTX-sensitive sodium channels, rather than from an enhancement of potassium conductance. Circ Res 50: 17-27, 1982