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Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity.
Higerd-Rusli, Grant P; Tyagi, Sidharth; Baker, Christopher A; Liu, Shujun; Dib-Hajj, Fadia B; Dib-Hajj, Sulayman D; Waxman, Stephen G.
Afiliação
  • Higerd-Rusli GP; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT 06520.
  • Tyagi S; Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510.
  • Baker CA; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
  • Liu S; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516.
  • Dib-Hajj FB; Cellular and Molecular Physiology Graduate Program, Yale University School of Medicine, New Haven, CT 06520.
  • Dib-Hajj SD; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT 06520.
  • Waxman SG; Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A ; 120(11): e2215417120, 2023 03 14.
Article em En | MEDLINE | ID: mdl-36897973
Inflammation causes pain by shifting the balance of ionic currents in nociceptors toward depolarization, leading to hyperexcitability. The ensemble of ion channels within the plasma membrane is regulated by processes including biogenesis, transport, and degradation. Thus, alterations in ion channel trafficking may influence excitability. Sodium channel NaV1.7 and potassium channel KV7.2 promote and oppose excitability in nociceptors, respectively. We used live-cell imaging to investigate mechanisms by which inflammatory mediators (IM) modulate the abundance of these channels at axonal surfaces through transcription, vesicular loading, axonal transport, exocytosis, and endocytosis. Inflammatory mediators induced a NaV1.7-dependent increase in activity in distal axons. Further, inflammation increased the abundance of NaV1.7, but not of KV7.2, at axonal surfaces by selectively increasing channel loading into anterograde transport vesicles and insertion at the membrane, without affecting retrograde transport. These results uncover a cell biological mechanism for inflammatory pain and suggest NaV1.7 trafficking as a potential therapeutic target.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Axônios / Nociceptores Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Axônios / Nociceptores Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2023 Tipo de documento: Article