Figure 1. NO inhibits M-current and increases neuronal excitability. A, Exemplary perforated patch voltage-clamp recording from a TG neuron. The magnitude of the deactivating tail current (Ideac) when stepping from −30 to −60 mV was plotted against time. Bath application of SNAP (1 mm) and the M-channel inhibitor XE991 (3 μm) is indicated by the black bars. The voltage protocol and exemplary current traces are also shown. B, Mean data from experiments as in A, expressed as percentage change in M-current from basal (n = 12). C, Concentration dependence of SNAP-induced M-current inhibition in TG neurons. SNAP was applied at concentrations of 10 μm, 30 μm, 100 μm, 300 μm, or 1000 μm under conditions of perforated patch voltage clamp; an IC50 of 370 ± 14 μm was obtained from the fit shown. D, Exemplary voltage trace of a TG neuron in control conditions and in the presence of SNAP (500 μm) during a perforated patch current-clamp recording. The traces show voltage responses to +0.125 nA current injections (600 ms). E, Linear regression of the number of APs versus injected current (nA) was used to calculate the slope of neuronal firing (this parameter characterizes the input–output relationship of a neuron) in the absence (control) or presence of SNAP (100–500 μm, n = 6). F, Mean data of the change in resting membrane potential (ΔEm) following SNAP application at concentrations of 100 μm (n = 7), 300 μm (n = 8), or 500 μm (n = 6) ± pre-application of XE991 (3 μm, n = 9). G, Schematic showing the experimental protocol for CGRP release assay and cell treatments. H, Mean data from CGRP release assay (n = 3). In all parts error bars indicate SEM and significant difference indicated by *p ≤ 0.05.