Figure 6.

Na_V1.7 Modulates Somal Excitability of Human Nociceptors

(A) Left: representative image showing action potential firing of a DIV 60 iPSC nociceptor to incremental current injections. Note the inflection on the falling phase of the action potential. Right: rheobase derived from pooled data of healthy (119 cells), CIP (85 cells), corrected (33 cells), and Na_V1.7 KO (45 cells) groups. Kruskal-Wallis followed by post hoc Dunn’s test was used for all comparisons.

(B) Supra-threshold firing in response to prolonged depolarization current injection. Left: representative firing from a cell from each group. Right: pooled data from the same cells as (A). Two-way ANOVA followed by post hoc Sidak’s multiple comparison test.

(C) Left: representative trace of voltage-gated sodium (Na_V) current induced by step depolarization to 0mV from a holding potential of −100 mV. Right: quantification of maximal NaV current comparing HC1 (n = 31) and Na_V1.7 KO (n = 27) groups. Student’s unpaired t test.

(D) Left: representative traces of firing in response to 1 nA current injection given over 100–1000 ms in 100 ms increments. Right: quantification of firing across different slopes of current injection. Two-way ANOVA followed by post hoc Sidak’s multiple comparison test. (HC1, 44 cells, and Na_V1.7 KO, 54 cells). See also Figure S6.

All data represent mean ± SEM pooled from at least independent differentiations. ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.01 healthy versus CIP. ^#p < 0.05, ^##p < 0.01, ^###p < 0.001, ^####p < 0.0001 Na_V1.7 KO versus HC1 (parent clone). ⁺p < 0.05 corrected versus cCIP1.2 (parent clone).