Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9.
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.
Blum
Robert
R
Institut für Physiologie, Ludwig-Maximilians-Universität München, D-80336 München, Germany.
Kafitz
Karl W
KW
Konnerth
Arthur
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004553:Electric Conductivity; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D012530:Saxitoxin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors; D009479:Neuropeptides; D016372:RNA, Antisense; D012333:RNA, Messenger; C491886:SCN11A protein, human; C113705:Scn11a protein, rat; D015222:Sodium Channels; C071951:neurotrophin 5; D012530:Saxitoxin; D012964:Sodium; D020813:Receptor, trkB; C073922:neurotrophin 4