Fig. 8. Enhanced use-dependent block of Nav1.4 by isoflurane and halothane. ( A ) Representative current traces showing isoflurane ( left ) and halothane ( right; solid lines ) enhancement of use-dependent block of I Nacompared to control ( dotted lines ) from a holding potential of –120 mV. ( B ) Peak currents were normalized to the current of the first pulse (mean ± SEM; n = 3), plotted against pulse number, and fitted to a monoexponential function. Halothane (0.82 ± 0.06 mm) reduced the time constant of use-dependent decay ( τuse ) from 7.3 to 2.0 pulses, and isoflurane (0.85 ± 0.08 mm) reduced τusefrom 3.3 ± 0.02 to 1.6 ± 0.02 pulses (mean, n = 3). Halothane produced a significantly greater reduction in the plateau I Naamplitude (0.94 ± 0.02 to 0.63 ± 0.02) than isoflurane (0.90 ± 0.01 to 0.76 ± 0.01; P < 0.05 by paired t test, n = 3). Repetitive pulse protocol: 25-ms, 10-Hz test pulses from holding potential of –120 mV to peak activation voltage.