The effect of lidocaine on diastolic transmembrane currents determining pacemaker depolarization in cardiac Purkinje fibers.

We studied the effects of lidocaine (1-5 mg/liter) on the diastolic currents of sheep Purkinje fibers by the two-microelectrode voltage clamp technique to obtain additional information on how lidocaine decreases the slope of spontaneous diastolic depolarization of mammalian Purkinje fibers. During voltage clamps we measured both the magnitude and time course of activation and deactivation of the time- and voltage-dependent potassium "pacemaker current" (iK2), and also the steady state current-voltage relationship throughout the pacemaker voltage range. At a concentration of 1 mg/liter lidocaine had no effect on the amplitude of iK2. In contrast, at 5 mg/liter, lidocaine diminished the magnitude of iK2 throughout the voltage range of pacemaker depolarization. Lidocaine (1-5 mg/liter) had no effect on either (1) the transmembrane voltage at which iK2 is half-activated, (2) the reversal voltage for iK2, or (3) the kinetics of iK2. Lidocaine (1-5 mg/liter) increased the steady state outward transmembrane current. This effect of lidocaine can be attributed to a variable contribution from both an increase in time-independent outward potassium current (iK1) and a decrease in background inward current.