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. 2018 Nov 21;38(47):10180–10201. doi: 10.1523/JNEUROSCI.1049-18.2018

Figure 4.

Figure 4.

Electrophysiological properties of DRG neurons derived from WT and Nav1.7 cKO mice. A, Current-clamp recordings of small-diameter DRG neurons acutely isolated from either control (cre.neg) mice or Nav1.7 cKO (cre.pos) mice. Mice were dissected 7–9 weeks following tamoxifen dosing to ensure complete decay of Nav1.7 protein. Current was injected to maintain a resting membrane potential of −70 mV in these recordings. Cells were stimulated with depolarizing current pulses of increasing amplitude until the cell fired an AP. The overall shape of the AP did not differ between genotypes. B, AP threshold voltage was measured before and after adding 500 nm TTX. Neurons from Nav1.7 cKO mice have significantly more depolarized AP threshold voltages relative to neurons from control mice. Furthermore, TTX significantly shifted the AP threshold voltage to more depolarized voltages in control neurons but not Nav1.7 cKO neurons. C, Current threshold for firing an AP was measured before and after adding 500 nm TTX. Neurons from Nav1.7 cKO mice required significantly larger current pulses to fire an AP relative to neurons from control mice. Furthermore, TTX significantly increased the amount of current needed to fire an AP in control neurons but not Nav1.7 cKO neurons. D, Resting membrane potential, set to −70 mV before the addition of TTX, did not significantly change after adding 500 nm TTX. E, AP overshoot amplitude was measured before and after adding 500 nm TTX. No difference was observed between control and Nav1.7 cKO neurons; however, addition of TTX significantly decreased AP overshoot amplitude in control neurons but not Nav1.7 cKO neurons. F, The 10%–90% peak rise rate was measured before and after adding 500 nm TTX. No difference was observed between control and Nav1.7 cKO neurons; however, addition of TTX significantly decreased upstroke slope in control neurons but not Nav1.7 cKO neurons. G, AP half-width was measured before and after adding 500 nm TTX. No difference was observed between control and Nav1.7 cKO neurons; however, addition of TTX significantly increased AP half-width in control neurons but not Nav1.7 cKO neurons. Significance (paired two-tailed t test): *p < 0.05; ***p < 0.001; ###p < 0.001. Error bars indicate SEM.