RT Journal Article
SR Electronic
T1 Building sensory axons: Delivery and distribution of Na<sub>V</sub>1.7 channels and effects of inflammatory mediators
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaax4755
DO 10.1126/sciadv.aax4755
VO 5
IS 10
A1 Akin, Elizabeth J.
A1 Higerd, Grant P.
A1 Mis, Malgorzata A.
A1 Tanaka, Brian S.
A1 Adi, Talia
A1 Liu, Shujun
A1 Dib-Hajj, Fadia B.
A1 Waxman, Stephen G.
A1 Dib-Hajj, Sulayman D.
YR 2019
UL http://advances.sciencemag.org/content/5/10/eaax4755.abstract
AB 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.