Effect of lidocaine on membrane currents in rabbit sino-atrial node cells

The ionic mechanism of effect of lidocaine (50-500 micrograms/ml) on the rabbit sino-atrial node was investigated by recording transmembrane potentials and by voltage clamping by means of a two microelectrode technique. Small sino-atrial (SA) node preparations (0.2 X 0.2 mm) were used. At doses larger than 50 micrograms/ml, lidocaine reduced the amplitude of the action potential, the maximum diastolic potential and the maximum rate of depolarization in a dose-dependent manner. At the same time, lidocaine prolonged the action potential duration and the cycle length. At a higher dose, lidocaine induced sinus arrest (in 3 of 17 specimens at 300 micrograms/ml and in 15 of 17 specimens at 500 micrograms/ml). In voltage clamp experiments, lidocaine (50 micrograms/ml) reduced the time-dependent outward current (Ik) but did not affect the slow inward current (Is). At doses larger than 100 micrograms/ml, lidocaine reduced both currents in a dose-dependent manner. The inward current activated by hyperpolarization (Ih) was also reduced. Inactivation of Is (f infinity) and steady-state activation of Ik (p infinity) were unchanged. Lidocaine did not affect the decay time course of Is and Ik. These results suggest that lidocaine decreases Is and Ik and that this decrease is due to a reduction in conductance of these current systems.