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

Publication ,  Journal Article
Purcell, EK; Yang, A; Liu, L; Velkey, JM; Morales, MM; Duncan, RK
Published in: Stem Cell Res
January 2013

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

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Published In

Stem Cell Res

DOI

EISSN

1876-7753

Publication Date

January 2013

Volume

10

Issue

1

Start / End Page

29 / 35

Location

England

Related Subject Headings

  • Neurotrophin 3
  • Neurons
  • Nerve Tissue Proteins
  • Mice
  • Membrane Potentials
  • KCNQ Potassium Channels
  • Embryonic Stem Cells
  • Developmental Biology
  • Cell Line
  • Cell Differentiation
 

Citation

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Purcell, E. K., Yang, A., Liu, L., Velkey, J. M., Morales, M. M., & Duncan, R. K. (2013). BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells. Stem Cell Res, 10(1), 29–35. https://doi.org/10.1016/j.scr.2012.08.005
Purcell, Erin K., Amy Yang, Liqian Liu, J Matthew Velkey, Marti M. Morales, and R Keith Duncan. “BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells.Stem Cell Res 10, no. 1 (January 2013): 29–35. https://doi.org/10.1016/j.scr.2012.08.005.
Purcell EK, Yang A, Liu L, Velkey JM, Morales MM, Duncan RK. BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells. Stem Cell Res. 2013 Jan;10(1):29–35.
Purcell, Erin K., et al. “BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells.Stem Cell Res, vol. 10, no. 1, Jan. 2013, pp. 29–35. Pubmed, doi:10.1016/j.scr.2012.08.005.
Purcell EK, Yang A, Liu L, Velkey JM, Morales MM, Duncan RK. BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells. Stem Cell Res. 2013 Jan;10(1):29–35.

Published In

Stem Cell Res

DOI

EISSN

1876-7753

Publication Date

January 2013

Volume

10

Issue

1

Start / End Page

29 / 35

Location

England

Related Subject Headings

  • Neurotrophin 3
  • Neurons
  • Nerve Tissue Proteins
  • Mice
  • Membrane Potentials
  • KCNQ Potassium Channels
  • Embryonic Stem Cells
  • Developmental Biology
  • Cell Line
  • Cell Differentiation