BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells

摘要: Neurons resembling the spiral ganglion neurons (SGNs) of auditory nerve can be generated from embryonic stem cells through induced overexpression transcription factor Neurogenin-1 (Neurog1). While recapitulating this developmental pathway produces glutamatergic, bipolar reminiscent SGNs, these are functionally immature, being characterized by a depolarized resting potential and limited excitability. We explored effects two neurotrophins known to present in inner ear, brain derived neurotrophic (BDNF) neurotrophin-3 (NT-3), on electrophysiology following Neurog1 induction. Our data reveal significant reduction membrane (RMP) neurotrophin exposure, with BDNF producing more robust effect than NT-3. This was accompanied profound specific upregulation KCNQ4 subtype, where 9-fold increase observed quantitative PCR. The other neuronally expressed KCNQ subtypes (2, 3, 5) exhibited which 3-fold or less magnitude. Quantitative immunohistochemistry confirmed expression at protein level. show novel link between expression, yielding insight into restricted pattern channel play special roles setting etiology progressive high-frequency hearing loss.