Fig. 1.

EPAC1 or EPAC2 activity maintains SCI-induced hyperexcitability in dissociated small diameter rat DRG neurons recorded by whole-cell patch clamp 18–30 h after dissociation. DRG neurons were pretreated with either 10 µM CE3F4 or 5 µM ESI-05 for 15–20 min before recording. (A) Inhibition of EPAC1 or 2 attenuated the incidence of SCI-induced SA. The ratio above each bar denotes the number of neurons with SA/the number of neurons sampled. Statistical comparisons of SA incidence were made with Bonferroni-corrected Fisher’s exact tests on the indicated pairs. (B) Inhibition of EPAC1 or 2 reversed SCI-induced depolarization of RMP. (C) Inhibition of EPAC1 or 2 did not reverse SCI-induced reduction of AP voltage threshold. (D) Inhibition of EPAC1 attenuated the SCI-induced decrease in rheobase. Data shown as mean ± SEM. Overall significance determined with one way ANOVA (or Kruskal-Wallis for non-parametric data), followed by multiple comparisons with Dunn’s method. Control Naïve vs SCI rats were compared by Mann-Whitney U test. (E) Inhibition of EPAC1 or EPAC2 decreased the amplitude of DSFs recorded at rest in DRG neurons from SCI rats, especially at more depolarized RMPs. DSFs were binned according to RMP. Data are represented as mean ± SEM. The indicated statistical comparisons were performed with Kruskal-Wallis test followed by multiple comparisons with Dunn’s method for each trio of data at each bin of RMP. ANOVA, analysis of variance; DRG, dorsal root ganglion; DSF, depolarizing spontaneous fluctuation; EPAC, exchange protein activated by cAMP; RMP, resting membrane potential; SA, spontaneous activity; SCI, spinal cord injury; SEM, standard error of the mean.