Selective silencing of Na V1.7 decreases excitability and conduction in vagal sensory neurons

Yukiko Muroi, Fei Ru, Marian Kollarik, Brendan J. Canning, Stephen A. Hughes, Stacey Walsh, Martin Sigg, Michael J. Carr, Bradley J. Undem

Research output: Contribution to journalArticlepeer-review

Abstract

There has been much information learned in recent years about voltage gated sodium channel (Na V) subtypes in somatosensory pain signalling, but much less is known about the role of specific sodium channel subtypes in the vagal sensory system. In this study, we developed a technique using adeno-associated viruses (AAVs) to directly introduce shRNA against Na V1.7 subtype gene into the vagal sensory ganglia of guinea pigsin vivo. Na V1.7 gene expression in nodose ganglia was effectively and selectively reduced without influencing the expression of other sodium channel subtype genes including Na V1.1, 1.2, 1.3 1.6, 1.8, or 1.9. Using a whole cell patch-clamp technique, this effect on Na V1.7 gene expression coincided with a reduction in tetrodotoxin-sensitive sodium current, a requirement for much larger depolarizing stimulus to initiate action potentials, and reduction in repetitive action potential discharge. Extracellular recordings in the isolated vagus nerve revealed that the conduction of action potentials in sensory A- and C-fibres in many neurons was effectively abolished after Na V1.7 shRNA introduction. Moreover, bilateral Na V1.7 shRNA injected animals survived for several months and the vagal reflex behaviour, exemplified by citric acid-induced coughing, was significantly suppressed. These data indicate that selectively silencing Na V1.7 ion channel expression leads to a substantial decrease in neural excitability and conduction block in vagal afferent nerves.

Original languageEnglish (US)
Pages (from-to)5663-5676
Number of pages14
JournalJournal of Physiology
Volume589
Issue number23
DOIs
StatePublished - Dec 2011

ASJC Scopus subject areas

  • Physiology

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