Lidocaine inhibition of the hyperpolarization-activated current (I-f) in sinoatrial myocytes

The aim of this study was to provide information on the dose dependence and biophysical details of lidocaine blockade of the hyperpolarization-activat ed current (I-f) in the sinoatrial node. Isolated rabbit sinoatrial myocyte s were patch-clamped in the whole-cell configuration at 36 +/- 0.5 degrees C, in the presence of 1 mM Ba2+ and 2 mM Mn2+ to minimize contamination by K+ and Ca2+ currents, respectively. Lidocaine inhibited I-f dose-dependentl y with a maximal inhibition of 69.5% at 75 mu M and a half-maximal effect a t 38.2 mu M. Lidocaine reduced the conductance of fully activated I-f witho ut affecting the current reversal potential; the blocking effect was indepe ndent of membrane potential. Voltage dependence of I-f activation gating wa s not affected by lidocaine, whose effect was independent of use and rate. Lidocaine did not modify the time course of I-f activation. At therapeutic concentrations, lidocaine: significantly inhibited I,by reducing fully acti vated channel conductance. Lack of voltage and rate dependence of effect di fferentiates lidocaine from most of other blockers of this current.