Fig. 1. Effects of meperidine and lidocaine on axonal Na⁺currents. Traces show multiple channel Na⁺currents recorded in (A ) control and 100 and 300 μM meperidine, and (B ) control and 100 and 300 μM lidocaine and after wash. The pulse protocol is given in text. Traces represent averages of 20 recordings. Holding potential was set to −90 mV, and a 50-ms prepulse to −130 mV was applied to remove fast inactivation, followed by a 50-ms test pulse to −40 mV. Bath, Ri-TEA; pipette, Cs^Cli. (C ) Concentration dependence of Na⁺channel block by externally applied meperidine (circles) and lidocaine (diamonds) were derived from experiments as shown in A  and B . Fractional block was obtained by measuring the reduction of peak current and is plotted versus  concentration of meperidine and lidocaine, respectively. The cross marks half-maximal concentration (IC⁵⁰). (D ) Simultaneous application of meperidine and lidocaine. Ordinate gives apparent IC⁵⁰values of meperidine obtained from concentration–effect experiments for meperidine during which various concentrations of lidocaine (abscissa) were present. Dashed lines show the theoretical change of the apparent meperidine IC⁵⁰in dependence of the simultaneously present concentrations of lidocaine assuming models of either competition of both drugs for one binding site (equation 2) or of two independent binding sites (no change). Dotted lines give 95% confidence intervals for the data. (C  and D ) Error bars show SEM if larger than symbol size, and the number of experiments is given above each data point.