VOLTAGE-DEPENDENT AND CONCENTRATION-DEPENDENT EFFECTS OF LIDOCAINE ON CARDIAC NA CHANNEL AND CA CHANNEL GATING CHARGE MOVEMENTS

The effects of lidocaine, a local anesthetic and cardiac antiarrhythmic agent, were studied on cardiac nonlinear Na channel and Ca channel charge movements (gating currents) of 17-day-old embryonic chick ventricular myocytes. Gating currents were recorded following the blockade of all ionic currents and the subtraction of the linear capacity currents (-P/5). From a holding potential of -100 mV the ON charge movement (Q(ON)) displayed two kinetic components: a rapidly decaying component associated with Na channel gating, and a slower component associated with Ca channel gating. A depolarizing prepulse to -50 mV for 125 ms reduced the fast component of Q(ON), with little effect on the slower component. Similarly, 20 mu M lidocaine also reduced the fast component of Q(ON) (Na channel charge movement) and had little effect on the slower component (Ca channel charge movement). Higher concentrations of lidocaine (125 mu M) reduced both the fast and the slower components of Q(ON). The effects of either a prepulse to -50 mV, or 20 mu M lidocaine on the steady-state Q(ON)/V-m relationship were nearly identical. These results suggest that lidocaine ''blocks'' cardiac Na (ionic) currents by a reduction in the availability of Na channel charge movement (Q(ON)), and that this reduction is similar to that produced by voltage-dependent inactivation.