Fig. 5.
AAV plasmid encoding NaV1.7-CRS reduces NaV1.7 currents through an endocytic mechanism and decreases spontaneous activity in the spinal cord. (A) Current traces recorded from DRGs transfected with pAAV-SCR (blue, n = 12) or pAAV-NaV1.7-CRS (green, n = 12). (B) Summary plots of current density–voltage relationship fitted with Boltzmann curve, (C) peak current density, and (D) electrically isolated TTX-R currents. (E) Current traces from transfected DRG neurons treated with vehicle or 5 nM ProTx-II. (F) Summary plots of current density–voltage relationship fitted with Boltzmann curve and (G) peak current density. (H) Current traces from groups transfected with pAAV-SCR or pAAV-NaV1.7-CRS and treated with Pitstop2 (20 µM). (I) Summary plots of current density–voltage relationship and (J) peak current density. Values for biophysical parameters in SI Appendix, Table S3. n = 9 to 15 cells. (K) Traces of spontaneous excitatory postsynaptic currents (sEPSC) from rat substantia gelatinosa (SG) neurons transduced with AAV-SCR (blue) or AAV-NaV1.7-CRS (green). (L) Cumulative distribution and bar graph of sEPSC interevent intervals from NaV1.7-CRS transduced neurons. (M) Cumulative distribution and bar graph showing decreased sEPSC amplitude in AAV-NaV1.7-CRS-treated rat slices compared to control. Data expressed as means ± SEM. Mann–Whitney U test and Kruskal–Wallis tests (details in Dataset S1).