PMID- 17959796
OWN - NLM
STAT- MEDLINE
DCOM- 20071108
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 43
DP  - 2007 Oct 24
TI  - Regulation of Na(v)1.2 channels by brain-derived neurotrophic factor, TrkB, and 
      associated Fyn kinase.
PG  - 11533-42
AB  - Voltage-gated sodium channels are responsible for action potential initiation and 
      propagation in neurons, and modulation of their function has an important impact 
      on neuronal excitability. Sodium channels are regulated by a Src-family tyrosine 
      kinase pathway, and this modulation can be reversed by specifically bound 
      receptor phosphoprotein tyrosine phosphatase-beta. However, the specific tyrosine 
      kinase and signaling pathway are unknown. We found that the sodium channels in 
      rat brain interact with Fyn, one of four Src-family tyrosine kinases expressed in 
      the brain. Na(V)1.2 channels and Fyn are localized together in the axons of 
      cultured hippocampal neurons, the mossy fibers of the hippocampus, and cell 
      bodies, dendrites, and axons of neurons in many other brain areas, and they 
      coimmunoprecipitate with Fyn from cotransfected tsA-201 cells. Coexpression of 
      Fyn with Na(V)1.2 channels decreases sodium currents by increasing the rate of 
      inactivation and causing a negative shift in the voltage dependence of 
      inactivation. Reconstitution of a signaling pathway from brain-derived 
      neurotrophic factor (BDNF) to sodium channels via the tyrosine receptor kinase B 
      (TrkB)/p75 neurotrophin receptor and Fyn kinase in transfected cells resulted in 
      an increased rate of inactivation of sodium channels and a negative shift in the 
      voltage dependence of inactivation after treatment with BDNF. These results 
      indicate that Fyn kinase is associated with sodium channels in brain neurons and 
      can modulate Na(V)1.2 channels by tyrosine phosphorylation after activation of 
      TrkB/p75 signaling by BDNF.
FAU - Ahn, Misol
AU  - Ahn M
AD  - Department of Pharmacology, University of Washington, Seattle, Washington 
      98195-7280, USA.
FAU - Beacham, Daniel
AU  - Beacham D
FAU - Westenbroek, Ruth E
AU  - Westenbroek RE
FAU - Scheuer, Todd
AU  - Scheuer T
FAU - Catterall, William A
AU  - Catterall WA
LA  - eng
GR  - NS25704/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NAV1.2 Voltage-Gated Sodium Channel)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Scn2A protein, rat)
RN  - 0 (Sodium Channels)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.2 (Fyn protein, rat)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cells, Cultured
MH  - Hippocampus/metabolism/physiology
MH  - NAV1.2 Voltage-Gated Sodium Channel
MH  - Nerve Tissue Proteins/antagonists & inhibitors/*metabolism
MH  - Patch-Clamp Techniques
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-fyn/genetics/metabolism/*physiology
MH  - Rats
MH  - Receptor, trkB/genetics/*physiology
MH  - Signal Transduction/genetics/physiology
MH  - Sodium Channels/*metabolism
MH  - Tyrosine/metabolism
PMC - PMC6673213
EDAT- 2007/10/26 09:00
MHDA- 2007/11/09 09:00
PMCR- 2008/04/24
CRDT- 2007/10/26 09:00
PHST- 2007/10/26 09:00 [pubmed]
PHST- 2007/11/09 09:00 [medline]
PHST- 2007/10/26 09:00 [entrez]
PHST- 2008/04/24 00:00 [pmc-release]
AID - 27/43/11533 [pii]
AID - 3258664 [pii]
AID - 10.1523/JNEUROSCI.5005-06.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 Oct 24;27(43):11533-42. doi: 10.1523/JNEUROSCI.5005-06.2007.