title: A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A.
abstract: Neuropathic pain may be produced, at least in part, by the increased activity of primary afferent neurons. Studies have suggested that an accumulation of voltage-gated sodium channels at the site of peripheral nerve injury is a primary precursory event for subsequent afferent hyperexcitability. In this study, a human sodium channel (hPN3, SCN10A) has been cloned from the lumbar 4/5 dorsal root ganglia (DRG). Expression of hPN3 in Xenopus oocytes showed that this clone is a functional voltage-gated sodium channel. The amino acid sequence of hPN3 is most closely related to the rat PN3/SNS sodium channels which are expressed primarily in the small neurons of rat DRGs. The homologous relationship between rPN3 and hPN3 is defined by (i) a high level of sequence identity (ii) sodium currents that are highly resistant to tetrodotoxin (TTX) (iii) similar tissue distribution profiles and (iv) orthologous chromosomal map positions. Since rPN3/SNS has been implicated in nociceptive transmission, hPN3 may prove to be a valuable target for therapeutic agents against neuropathic pain.
authors.affiliation: Center for Biological Research, Neurobiology Unit, Roche Bioscience, 3401 Hillview Avenue, Palo Alto, CA 94304, USA Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284, USA Formerly of Syntex (USA) Inc, 3401 Hillview Avenue, Palo Alto, CA 94304, USA.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Rabert
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Koch
authors.forename: Mariola
authors.initials: M
authors.lastname: Ilnicka
authors.forename: Rena A
authors.initials: RA
authors.lastname: Obernolte
authors.forename: Susan L
authors.initials: SL
authors.lastname: Naylor
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Herman
authors.forename: Richard M
authors.initials: RM
authors.lastname: Eglen
authors.forename: John C
authors.initials: JC
authors.lastname: Hunter
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Sangameswaran
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014018:Tissue Distribution; D014981:Xenopus
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568317:SCN10A protein, human; C568319:Scn10a protein, rat; D015222:Sodium Channels