Data for: Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli, Grant et al. (2023), Data for: Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity, Dryad, Dataset, https://doi.org/10.5061/dryad.hx3ffbgjg
Inflammation causes pain by shifting the balance of ionic currents in nociceptors towards 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 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.
Rehabilitation Research and Development Service, Award: B9253-C
Biomedical Laboratory Research and Development, VA Office of Research and Development, Award: BX004899
National Institute of Neurological Disorders and Stroke, Award: 1F31NS122417-01
National Institute of General Medical Sciences, Award: T32GM007205