Fig. 9.

p38 MAPK modulates voltage dependence of slow inactivation. A: voltage dependence of slow inactivation of TTX-r sodium currents, expressed as peaks of TTX-r sodium currents during a step to 0 mV, normalized to I_max (fraction available, means ± SE) and plotted against conditioning voltages before (gray squares) and 3 min after application of SB202190 (open circles, paired t-test, P < 0.05, n = 7. See Table 2 for the values of the V_1/2 and slope and statistical analysis). Inset: representative families of TTX-r sodium currents, recorded in the presence of TTX, elicited by 150-ms, 10-mV steps from a holding potential of −70 mV before (gray) and 3 min after application of SB202190 (black). Currents are adjusted according to the baseline before the activation step. The dashed line indicates the zero current level. The dotted line indicates the peak current level before application of SB202190. B: the ratio of peak TTX-r sodium current before application of treatment (I_Na,before) to the peak current after application (I_Na,treatment) of vehicle (n = 11) or SB202190 alone (n = 6). Values are means ± SE; **P < 0.01, one sample t-test comparing the values before and after the application of treatment. C: voltage dependence of slow inactivation of TTX-r sodium currents, expressed as peaks of TTX-r sodium currents during steps to 0 mV, normalized to I_max (fraction available, means ± SE) and plotted against conditioning voltages, measured 30 min after pretreatment with the p38 MAPK activator anisomycin (open circles, n = 26) or vehicle (black squares, n = 20), P < 0.01, two-sampled t-test; see also Table 3 for numerical data. Inset: histograms of the distribution of the values of V_1/2 of voltage dependence of slow inactivation of TTX-r sodium currents, recorded form neurons preincubated for 30 min with vehicle (gray, n = 20) or 10 μg/ml anisomycin (white, n = 26). Fitting of the distribution with the amplitude version of Gaussian peak function, y = y₀ + A × exp(−0.5 × {[V_1/2 − V_1/2(c)]/w})², where A is the peak number of cells and V_1/2(c) is the value of V_1/2 which corresponds to A; black solid line for vehicle; gray solid line for anisomycin, reveals that anisomycin produced substantial rightward shift of population of V_1/2 values [V_{1/2(c),Vehicle} = −30.3 ± 1.5 mV; V_{1/2(c),Anisomycin} = −21.2 ± 0.9 mV]. D: the peak TTX-r current density, measured from currents elicited by depolarizing steps to 0 mV from a holding potential of −70 mV, in cells pretreated with anisomycin or vehicle. Values are means ± SE, *P < 0.01, two sampled t-test, n = 26 for anisomycin group, n = 20 for vehicle group.