Fig. 1.

5-HT4 receptor agonist prucalopride (Ppr) induces long-term hyperexcitability (LTH) in small (≤30 µm soma diameter) sensory neurons. A, Experimental design (created with BioRender.com). All inhibitor studies co-applied Ppr with an inhibitor, except for one study in which the inhibitor was applied after washout of Ppr. B-E, Long-term effects on excitability of treatment with Ppr (1  µM) versus vehicle (0.01 % DMSO). Representative 10-s recordings at RMP B), or held under current clamp at −45 mV (D). Corresponding proportions of neurons exhibiting any AP discharge at RMP (SA), C) or at −45 mV (OA), E). Above each bar is the number of neurons exhibiting discharge over the total number sampled. Comparisons using Fisher’s exact test with p values reported above each bar. Red arrows indicate the largest subthreshold depolarizing spontaneous fluctuation (DSF) in each trace. F-H, Impact of 6-h Ppr treatment on other measures of excitability, RMP (F), AP voltage threshold (G), and rheobase (H). Datasets are graphed as mean ± SEM. Each circle represents the mean value for that condition per day of recording when both vehicle and prucalopride were tested. Comparisons used paired t-tests with p values reported in each panel. p < 0.05 was considered significant. AP, action potential; DRG, dorsal root ganglion; MP, membrane potential; N.S., non-significant; OA, ongoing activity; RMP, resting membrane potential; SA, spontaneous activity; Veh, vehicle. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)