Fig. 3.
Disruption of the NaV1.7-CRMP2 interaction decreases presynaptic NaV1.7, sensory neuron excitability, and spinal cord neurotransmitter release. (A) Representative action potential recordings from DRGs in response to current injections after adding Myr-TAT-SCR (blue) and Myr-TAT-NaV1.7-CRS peptides (green). (B) Quantification of current-evoked action potentials in response to 0 to 120 pA of injected current. (C) Resting membrane potential of cells recorded in A. (D) Representative traces and (E) quantification indicating an increased rheobase with Myr-TAT-NaV1.7-CRS treatment. n = 26 cells; (F) Summary data for membrane input resistance. (G) Immunoblots of NaV1.7, CRMP2, and CaV2.2 expression in the presynaptic fraction of spinal dorsal horn, 1 h after peptide injection [i.t. injection of 20 µg/5 µL of Myr-TAT-SCR (n = 6) or Myr-TAT-NaV1.7-CRS (n = 5)]. (H) Quantification showing NaV1.7 spinal presynaptic localization of data in G. (I) KCl depolarization-evoked CGRP release measured from isolated spinal cord following incubation with control, Myr-TAT-SCR, or Myr-TAT-NaV1.7-CRS peptides. Histograms show normalized CGRP levels (n = 4 animals); error bars indicate mean ± SEM; data analyzed by Mann–Whitney U test or two-way ANOVA (details in Dataset S1), P values indicated.