Figure 9.

p75^NTR is upregulated by a mechanism requiring membrane depolarization and opening of voltage-gated Ca²⁺-channels. a–c, Data obtained as in Figure 4d. a, Application of BAPTA-AM (intracellular calcium chelator) as well as of Ni²⁺/Cd²⁺ (blocker of voltage-gated calcium channels) prevented posttraumatic upregulation of p75^NTR. n = 29 slices/3290 neurons; **p = 0.041 (lesioned control)/0.039 (lesioned plus TrkB-Fc), one-way ANOVA and Bonferroni's post hoc analyses. b, Application of voltage-gated Na⁺ channel blocker TTX partly reduced the upregulation of p75^NTR. Adding GABA_A agonist muscimol in the presence of TTX restored the level of p75^NTR to the level of lesioned control; the effect of muscimol could be abolished by bumetanide. Adding GABA_A antagonist bicuculline in the presence of TTX completely abolished the increase in p75^NTR. Applying K⁺ channel blocker 4-AP in the presence of bumetanide did not result in the significant increase in the number of p75^NTR-positive neurons; n = 128 slices/13,600 neurons; **p = 0.037 (lesioned control)/0.019 (lesioned plus TTX plus muscimol), one-way ANOVA and Bonferroni's post hoc analyses. c, Application of KCl and TTX to induce membrane depolarization in the absence of action potential firing upregulated p75^NTR in nonaxotomized slices; the effect could be blocked by Ni²⁺/Cd²⁺; n = 48 slices/5490 neurons; ***p = 0.001, one-way ANOVA and Bonferroni's post hoc analyses. Error bars indicate SEM.