Figure 13.

M-current blockade occludes the change in firing pattern induced by p75 activation. A, Superimposed raw current traces recorded in voltage clamp from a cultured sympathetic neuron in response to steps from −30 mV to −50 mV showing that application of 12.5 μm linopirdine decreased the M-type current (black trace versus dark gray trace). This decrease partially reversed after a 15 min wash (light gray trace). B, A plot of spike output versus test step amplitude shows that application of the M-current blocker, 12.5 μm linopirdine with C₂-ceramide (open triangles, n = 9), blocked the C₂-ceramide-induced decrease in spike output (gray line; p < 0.01, two-way ANOVA, followed by the Tukey test). Application of linopirdine alone (filled circles) caused a trend toward increased spike output compared with saline (black line), which did not reach statistical significance. C, Bar plots of the percentage of spikes occurring in the second half of the stimulus shows that linopirdine alone significantly promoted tonic firing (filled bar versus dark gray bar; p < 0.05, Kruskal–Wallis ANOVA on ranks, followed by Dunn's test). Linopirdine decreased the ability of ceramide to promote phasic firing (ceramide, open bar compared with linopirdine/ceramide, gray bar; p < 0.05, Kruskal–Wallis ANOVA on ranks, followed by Dunn's test).