A voltage‐clamp study of the effect of two lidocaine derivatives on the time course of end‐plate currents.

Abstract

Voltage-clamped end-plate currents (epc) were studied in the gylcerol-treated Rana pipiens sartorius nerve-muscle preparations in normal Ringer solution and in the presence of QX-222 [2-(trimethylamino)-N-2,6-dimethylphenylacetamide] and QX-314 [2-(triethylamino-N-2,6-dimethylphenylacetamide]. Both QX-222 and QX-314, the trimethyl and triethyl analogs, respectively, of lidocaine, greatly modify end-plate current kinetics. The altered epc still show a true reversal potential, which is essentially the same as the reversal potential before drug treatment. The time course of the altered end-plate currents varies with both membrane potential and drug concentration. In the presence of 0.1-1.0 mM QX-222, end-plate currents decay as the sum of 3 exponentials: I(t) = I1(0)e-k1t + I2(0)e-k2t + I3(0)e-k3t, where the subscripts 1, 2 and 3 refer to the rapidly, intermediately, and slowly decaying components, respectively. Both the amplitudes, Ij(0), and the decay rates, kj, depend upon membrane potential. Hyperpolarization increases the relative size of the 1st and 3rd components, i.e., I1(0) and I3(0) increase relative to I2(0). Depolarization increases the relative size of the 2nd component. Hyperpolarization causes a decrease in the decay rates k2 and k3 and causes a slight increase in the decay rate k1. Dependence of the 3 decay rates on membrane potential is well described by: kj = bjeajV. The Q10 of each of the kj is about 3. Raising QX-222 concentration, at any given membrane potential, augments I1(0) and I3(0) at the expense of I2(0). Raising concentration increases k1 and decreases k3; their voltage-dependence is little affected. At all QX-222 concentrations tested the decay rate k2 is nearly the same as the decay rate of a normal epc recorded at an equivalent holding potential from the same fiber before drug exposure. End-plate currents in the presence of 0.1 mM QX-314 show a major or rapidly decaying phase and a very small, slowly decaying phase or tail, but no intermediate component. Only the major component is discernible for end-plate currents in 0.5 mM QX-314. Voltage- and concentration-dependence of the decay rate of the major component in QX-314 is similar to k1 in QX-222. Voltage-dependence of the tail''s decay rate appears to be similar to k3. The 2nd component in QX-222 may represent currents of unaltered or normal conductance kinetics, and that the 1st and 3rd components in QX-222, as well as the major component and tail in QX-314, represent current of QX-altered conductance kinetics.