Fig. 8. Comparison of the state-dependent binding rates of imipramine and carbamazepine. (A ) The macroscopic binding rates of imipramine or carbamazepine are examined at holding potentials (Vh) of −120 and −55 mV, where most Na+channels stay at the resting and the inactivated states, respectively. The neuron was stepped to 0 mV for 17 ms after the designated holding potential every 1 or 0.5 s to continuously elicit Na+currents and quickly moved between the control (Tyrode's solution) and the drug (carbamazepine or imipramine)-containing solutions. When a neuron was exposed to carbamazepine or imipramine, the elicited current was reduced in a time-dependent manner. We plot the time-dependent reduction of the current amplitude and fit the time courses with a monoexponential function. Only raw data that are readily reversible are collected. The number of measurement is given beside each data point in the figure. The inverse of the time constant form the monoexponential fitting is then plotted against drug concentration. The data are fitted with a regression line with the assumption of one-to-one binding to obtain the macroscopic binding rates, which are 0.35 ± 0.15 × 104, 11.7 ± 0.47 × 104, 3.4 ± 1.6 × 104, and 3.5 ± 0.08 × 104M−1· s−1for carbamazepine (Vh =−120 mV), carbamazepine (Vh =−55 mV), imipramine (Vh =−120 mV), and imipramine (Vh =−55 mV), respectively. (B ) Comparison between the macroscopic binding rates of imipramine and carbamazepine to the resting (R, Vh =−120 mV) and inactivated (I, Vh =−55 mV) states from the experiments described in A . The binding rates to the resting and inactivated states are similar for imipramine but are apparently dissimilar for carbamazepine.