Selective inhibition of vagal afferent nerve pathways regulating cough using NaV 1.7 shRNA silencing in guinea pig nodose ganglia

Yukiko Muroi, Fei Ru, Yang Ling Chou, Michael J. Carr, Bradley J. Undem, Brendan J. Canning

Research output: Contribution to journalArticle

Abstract

Adeno-associated virus delivery systems and short hairpin RNA (shRNA) were used to selectively silence the voltage-gated sodium channel NaV 1.7 in the nodose ganglia of guinea pigs. The cough reflex in these animals was subsequently assessed. NaV 1.7 shRNA was delivered to the majority of nodose ganglia neurons [50-60% transfection rate determined by green fluorescent protein (GFP) gene cotransfection] and action potential conduction in the nodose vagal nerve fibers, as evaluated using an extracellular recording technique, was markedly and significantly reduced. By contrast, <5% of neurons in the jugular vagal ganglia neurons were transfected, and action potential conduction in the jugular vagal nerve fibers was unchanged. The control virus (with GFP expression) was without effect on action potential discharge and conduction in either ganglia. In vivo, NaV 1.7 silencing in the nodose ganglia nearly abolished cough evoked by mechanically probing the tracheal mucosa in anesthetized guinea pigs. Stimuli such as capsaicin and bradykinin that are known to stimulate both nodose and jugular C-fibers evoked coughing in conscious animals was unaffected by NaV 1.7 silencing in the nodose ganglia. Nodose C-fiber selective stimuli including adenosine, 2-methyl-5-HT, and ATP all failed to evoke coughing upon aerosol challenge. These results indicate that cough is independently regulated by two vagal afferent nerve subtypes in guinea pigs, with nodose Aδ fibers regulating cough evoked mechanically from the trachea and bradykinin- and capsaicin-evoked cough regulated by C-fibers arising from the jugular ganglia.

Original languageEnglish (US)
Pages (from-to)R1017-R1023
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume304
Issue number11
DOIs
StatePublished - Jun 10 2013

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Keywords

  • C-fibers
  • Capsaicin
  • Na 1.7
  • Sodium channels
  • Vagal reflex

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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