title: A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia.
abstract: Dorsal root ganglion neurons express a wide repertoire of sodium channels with different properties. Here, we report the cloning from rat, dorsal root ganglia (DRG), cellular expression, and functional analysis of a novel tetrodotoxin-sensitive peripheral sodium channel (PN), PN1. PN1 mRNA is expressed in many different tissues. Within the rat DRG, both the mRNA and PN1-like immunoreactivity are present in small and large neurons. The abundance of sodium channel mRNAs in rat DRG is rBI > PN1 >/= PN3 >>> rBIII by quantitative reverse transcription-polymerase chain reaction analysis. Data from reverse transcription-polymerase chain reaction and sequence analyses of human DRG and other human tissues suggest that rat PN1 is an ortholog of the human neuroendocrine channel. In Xenopus oocytes, PN1 exhibits kinetics that are similar to rBIIa sodium currents and is inhibited by tetrodotoxin with an IC50 of 4.3 +/- 0.92 nM. Unlike rBIIa, the inactivation kinetics of PN1 are not accelerated by the coexpression of the beta-subunits.
authors.affiliation: Center for Biological Research, Neurobiology Unit, Roche Bioscience, Palo Alto, California 94304, USA. lakshmi.sangameswaran@roche.com
authors.forename: L
authors.initials: L
authors.lastname: Sangameswaran
authors.forename: L M
authors.initials: LM
authors.lastname: Fish
authors.forename: B D
authors.initials: BD
authors.lastname: Koch
authors.forename: D K
authors.initials: DK
authors.lastname: Rabert
authors.forename: S G
authors.initials: SG
authors.lastname: Delgado
authors.forename: M
authors.initials: M
authors.lastname: Ilnicka
authors.forename: L B
authors.initials: LB
authors.lastname: Jakeman
authors.forename: S
authors.initials: S
authors.lastname: Novakovic
authors.forename: K
authors.initials: K
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Sze
authors.forename: E
authors.initials: E
authors.lastname: Tzoumaka
authors.forename: G R
authors.initials: GR
authors.lastname: Stewart
authors.forename: R C
authors.initials: RC
authors.lastname: Herman
authors.forename: H
authors.initials: H
authors.lastname: Chan
authors.forename: R M
authors.initials: RM
authors.lastname: Eglen
authors.forename: J C
authors.initials: JC
authors.lastname: Hunter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005727:Ganglia, Spinal / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides; D009865:Oocytes / Q000502:physiology; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015222:Sodium Channels / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014158:Transcription, Genetic; D014982:Xenopus laevis
chemical_list: D018076:DNA, Complementary; D046911:Macromolecular Substances; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D012333:RNA, Messenger; C486866:SCN9A protein, human; C503480:Scn9a protein, rat; D015222:Sodium Channels; D013779:Tetrodotoxin