Figure 5. I_NaP-blockers or a KCC2-enhancer normalize the excitability of the spinal cord below SCI.

(A,D,F,I,K,N) Representative L5 ventral root activities (VR L5) evoked by a supramaximal stimulation (St.) of the ipsilateral dorsal root (A,F,K) or occurring spontaneously (D,I,N) in spinal cords isolated from SCI rats (4–5 d post-SCI) before (black) and after bath-applying 5 µM riluzole (A,D); red, 30 min, n = 8 rats), 200 nM 4,9-ah-TTX (F,I; blue, 30 min, n = 15 rats for F, n = 20 rats for I) or 10 µM PCPz (K,N; green, 30 min, n = 9 rats for K, n = 11 rats for N). Insets in (A,F,K) illustrate enlargements of the monosynaptic response. (B,G,L) Average peristimulus time histogram (PSTH, bin width: 20 ms) of dorsal root evoked L5 ventral root responses before (black) and after (color) bath-applying the above-mentioned drugs. (C,E,H,J,M,O) Group means quantification of: the monosynaptic reflex and events per rat detected over time windows of 10–40 ms and 500–15,000 ms post-stimulus for SLR and LLR, respectively (C,H,M), and spontaneous activities (E,J,O). *p<0.05, **p<0.01, ***p<0.001, comparing data collected before and after adding drugs mentioned above; Wilcoxon paired test. Data are mean ± SD. Underlying numerical values can be found in the Figure 5—source data 1.

Figure 5—figure supplement 1. The I_NaP-enhancer veratridine used at 100 nM triggers riluzole-sensitive hyperreflexia and spontaneous activities in isolated spinal cords from intact neonatal rats.

(A,D) Representative L5 ventral root activities (VR L5) evoked by a supramaximal stimulation (St.) of the ipsilateral dorsal root (A) or occurring spontaneously (D) in spinal cords isolated from intact rats (4–5 d-old; n = 8 rats) before (black) and after (red) bath-applying veratridine alone (100 nM) and then superfused with riluzole (5 µM, gray). (B) Average peristimulus time histogram (PSTH, bin width: 20 ms) of dorsal root evoked L5 ventral root. (C) Group means quantification of: the monosynaptic reflex and events per rat detected over time windows of 10–40 ms and 500–15,000 ms post-stimulus for SLR and LLR, respectively. *p<0.05, **p<0.01; One-way ANOVA. (E) Group means quantification of spontaneous activities. *p<0.05; Wilcoxon paired test. Underlying numerical values can be found in the Figure 5—figure supplement 1—source data 1.

Figure 5—figure supplement 2. I_CaP does not contribute to hyperexcitability caudal to SCI.

(A,D,F,I) Representative L5 ventral root activities (VR L5) evoked by a supramaximal stimulation (St.) of the ipsilateral dorsal root (A,F) or occurring spontaneously (D,I) before (black) and after bath-applying 20 µM nifedipine in spinal cords isolated from SCI rats (A,D, 4–5 d post-SCI, orange, 30 min, n = 14 rats), or 10 µM Bay-K in spinal cords isolated from intact rats (F,I, 4–5 d-old, blue, 30 min, n = 7 rats). Insets in A,F illustrate enlargements of the monosynaptic response. (B,G) Average peristimulus time histogram (PSTH, bin width: 20 ms) of dorsal root evoked L5 ventral root responses before (black) and after (color) bath-applying the above-mentioned drugs. (C,E,H,J) Group means quantification of: the monosynaptic reflex and events per rat detected over time windows of 10–40 ms and 500–15,000 ms post-stimulus for SLR and LLR, respectively (C,H), and spontaneous activities (E,J). *p<0.05, **p<0.01, ***p<0.001, comparing data collected before and after adding drugs mentioned above; Wilcoxon paired test. Data are mean ± SD. Underlying numerical values can be found in the Figure 5—figure supplement 2—source data 1.