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Regulation of Na(v)1.2 channels by brain-derived neurotrophic factor, TrkB, and associated Fyn kinase.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2007 Oct 24; Vol. 27 (43), pp. 11533-42. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Cells, Cultured
Hippocampus metabolism
Hippocampus physiology
NAV1.2 Voltage-Gated Sodium Channel
Nerve Tissue Proteins antagonists & inhibitors
Patch-Clamp Techniques
Phosphorylation
Proto-Oncogene Proteins c-fyn genetics
Proto-Oncogene Proteins c-fyn metabolism
Rats
Receptor, trkB genetics
Signal Transduction genetics
Signal Transduction physiology
Tyrosine metabolism
Brain-Derived Neurotrophic Factor physiology
Nerve Tissue Proteins metabolism
Proto-Oncogene Proteins c-fyn physiology
Receptor, trkB physiology
Sodium Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 27
- Issue :
- 43
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 17959796
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.5005-06.2007