Figure 8. Use-dependent block of sodium currents by volatile anesthetics (desflurane shown as an example). Trains of 20 depolarizations from -85 to 0 mV at 5 Hz were applied. On perfusion with desflurane, the current is increasingly suppressed during the pulse train. (A) Voltage protocol and current traces elicited by the first and last pulse before and during superfusion with 2.6 mM desflurane. (B) Peak sodium currents plotted versus pulse number, before (circles) and during superfusion with 1.3 mM (diamonds), 2.6 mM (squares), and 5.3 mM (triangles) desflurane. Same cell as in (A). Lines are least-squares fits to a single exponential function: I sub (t) = I^omega+ {(I¹- I^omega)*exp(-[t - 1]/tau)}, yielding the parameters I¹, the current of the first pulse; I^omega, the limiting current at the n-th pulse; and tau, the time constant. Time constants for use-dependent block at 1.3, 2.6, and 5.3 mM desflurane are 6.0, 3.2 and 2.7 ms, respectively. The I^omega/I¹-ratios for the respective concentrations are 0.84, 0.72, and 0.45.