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International Association for the Study of Pain

Dynamic Regulation of Axonal Trafficking of Ion Channels in Sensory Neurons

Topical Workshop
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Topical Workshop

10:45 am

07 September 2023

Auditorium IV

New Approaches to Advance Studies in Pain Pathophysiology and Pharmacology

Intended Audiences

Cross-disciplinary

Abstract Description

Changes in excitability of sensory neurons are heavily linked to the onset and maintenance of pain. Neuronal excitability relies on coordinated action of functionally distinct ion channels; voltage-gated sodium (NaV) channels provide depolarizing current, and potassium (KV) channels provide hyperpolarizing current. Mutations and dysfunction of multiple NaV and KV channels underlie disorders of excitability, including pain. Modulating ion channel trafficking may offer a potential therapeutic strategy for these diseases. However, little is known about molecules and mechanisms that control ion channel trafficking and surface distribution along the length of sensory axons, and their dynamic regulation under disease and injury conditions. Our new platform, Optical Pulse chase Axonal Long distance (OPAL) imaging, enables real-time imaging of ion channels within living sensory neurons at a distance from the soma with unprecedented spatial- and temporal-resolution. Using this method, we have investigated long-distance axonal trafficking of NaV and KV channels and their fate at the plasma membrane. We show that multiple ion channel subtypes are transported together in axonal vesicles. Using Nav1.7 as a target, we show that internalized channels are recycled to the axonal, but not soma, membranes, and demonstrate differential effects of inflammatory mediators on the trafficking of Nav1.7 and kv7.2 channels. 

Presenters

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