Building sensory axons: Delivery and distribution of NaV1.7 channels and effects of inflammatory mediators.

Abstract

Sodium channel NaV1.7 controls firing of nociceptors, and its role in human pain has been validated by genetic and functional studies. However, little is known about NaV1.7 trafficking or membrane distribution along sensory axons, which can be a meter or more in length. We show here with single-molecule resolution the first live visualization of NaV1.7 channels in dorsal root ganglia neurons, including long-distance microtubule-dependent vesicular transport in Rab6A-containing vesicles. We demonstrate nanoclusters that contain a median of 12.5 channels at the plasma membrane on axon termini. We also demonstrate that inflammatory mediators trigger an increase in the number of NaV1.7-carrying vesicles per axon, a threefold increase in the median number of NaV1.7 channels per vesicle and a ~50% increase in forward velocity. This remarkable enhancement of NaV1.7 vesicular trafficking and surface delivery under conditions that mimic a disease state provides new insights into the contribution of NaV1.7 to inflammatory pain.

• Authors: Elizabeth J Akin, Grant P Higerd-Rusli, Malgorzata A Mis, Brian S Tanaka, Talia Adi, Shujun Liu, Fadia B Dib-Hajj, Stephen G Waxman, Sulayman D Dib-Hajj
• Journal: Science advances (Sci Adv) Vol. 5 Issue 10 Pg. eaax4755 (10 2019) ISSN: 2375-2548 [Electronic] United States
• PMID: 31681845 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

• Fluorescent Dyes
• Inflammation Mediators
• NAV1.7 Voltage-Gated Sodium Channel
• Rab6 protein
• rab GTP-Binding Proteins

Topics

• Animals
• Axons (metabolism)
• Cell Membrane (metabolism)
• Fluorescent Dyes (metabolism)
• Ganglia, Spinal (metabolism)
• Humans
• Inflammation (pathology)
• Inflammation Mediators (metabolism)
• Ion Channel Gating
• Mice
• NAV1.7 Voltage-Gated Sodium Channel (metabolism)
• Pain (pathology)
• Rats
• Sensory Receptor Cells (metabolism)
• rab GTP-Binding Proteins (metabolism)