PMID- 12384689 OWN - NLM STAT- MEDLINE DCOM- 20021108 LR - 20161124 IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 419 IP - 6908 DP - 2002 Oct 17 TI - Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9. PG - 687-93 AB - 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. FAU - Blum, Robert AU - Blum R AD - Institut fur Physiologie, Ludwig-Maximilians-Universitat Munchen, D-80336 Munchen, Germany. FAU - Kafitz, Karl W AU - Kafitz KW FAU - Konnerth, Arthur AU - Konnerth A LA - eng SI - GENBANK/AF059030 SI - GENBANK/AF109737 SI - GENBANK/AJ417790 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (NAV1.9 Voltage-Gated Sodium Channel) RN - 0 (Nerve Growth Factors) RN - 0 (Neuropeptides) RN - 0 (RNA, Antisense) RN - 0 (RNA, Messenger) RN - 0 (SCN11A protein, human) RN - 0 (Scn11a protein, rat) RN - 0 (Sodium Channels) RN - 145172-44-7 (neurotrophin 5) RN - 35523-89-8 (Saxitoxin) RN - 9NEZ333N27 (Sodium) RN - EC 2.7.10.1 (Receptor, trkB) RN - P658DCA9XD (neurotrophin 4) SB - IM CIN - Nature. 2002 Oct 17;419(6908):683-4. PMID: 12384684 MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Line MH - Cells, Cultured MH - Cloning, Molecular MH - Electric Conductivity MH - Hippocampus/cytology/drug effects/metabolism MH - Humans MH - Molecular Sequence Data MH - NAV1.9 Voltage-Gated Sodium Channel MH - Nerve Growth Factors/*pharmacology MH - Neuroblastoma MH - Neurons/drug effects/metabolism MH - Neuropeptides/genetics/*metabolism MH - RNA, Antisense/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, trkB/genetics/metabolism MH - Saxitoxin/pharmacology MH - Sodium/metabolism MH - Sodium Channels/genetics/*metabolism EDAT- 2002/10/18 04:00 MHDA- 2002/11/26 04:00 CRDT- 2002/10/18 04:00 PHST- 2002/04/29 00:00 [received] PHST- 2002/08/13 00:00 [accepted] PHST- 2002/10/18 04:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/10/18 04:00 [entrez] AID - nature01085 [pii] AID - 10.1038/nature01085 [doi] PST - ppublish SO - Nature. 2002 Oct 17;419(6908):687-93. doi: 10.1038/nature01085.