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

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

Research output: Contribution to journalArticlepeer-review

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 2019

Keywords

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'The voltage-gated sodium channel Na<sub>V</sub>1.8 blocker A-803467 inhibits cough in the guinea pig'. Together they form a unique fingerprint.

Cite this