Abstract
Brain-derived neurotrophic factor (BDNF) and other neurotrophins are essential for normal brain function. Many types of neurons in the central nervous system are excited by BDNF or neurotrophin-4/5, an action that has recently been implicated in synaptic plasticity. The mechanisms involved in this transmitter-like action of neurotrophins remains unclear. Here, by screening candidate genes with an antisense messenger RNA expression approach and by co-expressing the receptor tyrosine kinase TrkB and various sodium channels, we demonstrate that the tetrodotoxin-insensitive sodium channel Na(V)1.9 underlies the neurotrophin-evoked excitation. These results establish the molecular basis of neurotrophin-evoked depolarization and reveal a mechanism of ligand-mediated sodium channel activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain-Derived Neurotrophic Factor / pharmacology
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Cell Line
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Cells, Cultured
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Cloning, Molecular
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Electric Conductivity
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / metabolism
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Humans
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Molecular Sequence Data
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NAV1.9 Voltage-Gated Sodium Channel
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Nerve Growth Factors / pharmacology*
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Neuroblastoma
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Neurons / drug effects
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Neurons / metabolism
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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RNA, Antisense / genetics
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RNA, Antisense / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptor, trkB / genetics
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Receptor, trkB / metabolism
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Saxitoxin / pharmacology
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Sodium / metabolism
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Sodium Channels / genetics
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Sodium Channels / metabolism*
Substances
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Brain-Derived Neurotrophic Factor
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NAV1.9 Voltage-Gated Sodium Channel
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Nerve Growth Factors
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Neuropeptides
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RNA, Antisense
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RNA, Messenger
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SCN11A protein, human
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Scn11a protein, rat
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Sodium Channels
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neurotrophin 5
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Saxitoxin
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Sodium
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Receptor, trkB
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neurotrophin 4
Associated data
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GENBANK/AF059030
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GENBANK/AF109737
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GENBANK/AJ417790