title: Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.
abstract: Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.
authors: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Chongyang
authors: C
authors: Han
authors: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Mark
authors: M
authors: Estacion
authors: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Jianying
authors: J
authors: Huang
authors: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Dymtro
authors: D
authors: Vasylyev
authors: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Peng
authors: P
authors: Zhao
authors: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Sulayman D
authors: SD
authors: Dib-Hajj
authors: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, Connecticut stephen.waxman@yale.edu.
authors: Stephen G
authors: SG
authors: Waxman
mesh_terms: D000368:Aged; D000818:Animals; D001703:Biophysics; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D014162:Transfection
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; C568317:SCN10A protein, human; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Nav1.8; dorsal root ganglion; persistent current; ramp current; sodium channel