The voltage-gated sodium channel NaV1.8 blocker A-803467 inhibits cough in the guinea pig

M. Brozmanova, S. Svajdova, N. Pavelkova, Y. Muroi, Bradley J Undem, M. Kollarik

Research output: Contribution to journalArticle

Abstract

Cough in respiratory diseases is attributed to the activation of airway C-fibers by inflammation. Inflammatory mediators can act on multiple receptors expressed in airway C-fibers, nonetheless, the action potential initiation in C-fibers depends on a limited number of voltage-gated sodium channel (NaV1) subtypes. We have recently demonstrated that NaV1.8 substantially contributes to the action potential initiation in the airway C-fiber subtype implicated in cough. We therefore hypothesized that the NaV1.8 blocker A-803467 inhibits cough. We evaluated the cough evoked by the inhalation of C-fiber activator capsaicin in awake guinea pigs. Compared to vehicle, intraperitoneal or inhaled A-803467 caused 30–50% inhibition of cough at the doses that did not alter respiratory rate. We conclude that the NaV1.8 blocker A-803467 inhibits cough in a manner consistent with its action on the C-fiber nerve terminals in the airways. Targeting voltage-gated sodium channels mediating action potential initiation in airway C-fibers may offer a means of cough inhibition that is independent of the stimulus.

Original languageEnglish (US)
Article number103267
JournalRespiratory Physiology and Neurobiology
Volume270
DOIs
StatePublished - Dec 1 2019

Fingerprint

Voltage-Gated Sodium Channel Blockers
Unmyelinated Nerve Fibers
Cough
Guinea Pigs
Action Potentials
Voltage-Gated Sodium Channels
Capsaicin
Respiratory Rate
Inhalation
Inflammation

Keywords

  • Bronchopulmonary C-fibers
  • Cough
  • NaV1.8
  • Vagus nerve
  • Voltage-gated sodium channels

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

The voltage-gated sodium channel NaV1.8 blocker A-803467 inhibits cough in the guinea pig. / Brozmanova, M.; Svajdova, S.; Pavelkova, N.; Muroi, Y.; Undem, Bradley J; Kollarik, M.

In: Respiratory Physiology and Neurobiology, Vol. 270, 103267, 01.12.2019.

Research output: Contribution to journalArticle

Brozmanova, M. ; Svajdova, S. ; Pavelkova, N. ; Muroi, Y. ; Undem, Bradley J ; Kollarik, M. / The voltage-gated sodium channel NaV1.8 blocker A-803467 inhibits cough in the guinea pig. In: Respiratory Physiology and Neurobiology. 2019 ; Vol. 270.
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