title: Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons.
abstract: Erythromelalgia is an autosomal dominant disorder characterized by burning pain in response to warm stimuli or moderate exercise. We describe a novel mutation in a family with erythromelalgia in SCN9A, the gene that encodes the Na(v)1.7 sodium channel. Na(v)1.7 produces threshold currents and is selectively expressed within sensory neurons including nociceptors. We demonstrate that this mutation, which produces a hyperpolarizing shift in activation and a depolarizing shift in steady-state inactivation, lowers thresholds for single action potentials and high frequency firing in dorsal root ganglion neurons. Erythromelalgia is the first inherited pain disorder in which it is possible to link a mutation with an abnormality in ion channel function and with altered firing of pain signalling neurons.
authors.affiliation: Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Dib-Hajj
authors.forename: A M
authors.initials: AM
authors.lastname: Rush
authors.forename: T R
authors.initials: TR
authors.lastname: Cummins
authors.forename: F M
authors.initials: FM
authors.lastname: Hisama
authors.forename: S
authors.initials: S
authors.lastname: Novella
authors.forename: L
authors.initials: L
authors.lastname: Tyrrell
authors.forename: L
authors.initials: L
authors.lastname: Marshall
authors.forename: S G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004916:Erythromelalgia / Q000235:genetics* / Q000503:physiopathology; D005192:Family Health; D005260:Female; D005727:Ganglia, Spinal / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000503:physiopathology; D018408:Patch-Clamp Techniques / Q000379:methods; D010375:Pedigree; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D015222:Sodium Channels; D004247:DNA