Related Experiment Video
Updated: Aug 7, 2025

Teasing Out the Interplay Between Natural Killer Cells and Nociceptor Neurons
Published on: June 30, 2022
Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat
Grant P Higerd-Rusli1,2,3,4,5, Sidharth Tyagi1,2,3,4,6, Christopher A Baker2,3,4
1Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT 06520.
Abstract:
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.
Related Concept Videos
Nociception
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Nitric Oxide Signaling Pathway
Mechanically-gated Ion Channels
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...

