Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation

Research output: Contribution to journalArticle

Abstract

We tested the hypothesis that an ionic current carried by chloride ions contributes to bradykinin (BK)-induced membrane depolarization and activation of vagal afferent C-fibres. In an ex vivo innervated trachea/bronchus preparation, BK (1 μM) consistently produced action potential discharge in vagal afferent C-fibres with receptive fields in the trachea or main stem bronchus. The Ca2+-activated Cl- channel (CLCA) inhibitor, niflumic acid (NFA, 100 μM), significantly reduced BK-induced action potential discharge to 21 ± 7% of the control BK response. NFA did not inhibit capsaicin-induced or citric-acid-induced action potential discharge in tracheal C-fibres. The inhibitory effect of NFA was mimicked by another CLCA inhibitor, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB, 100 μM). NFA also inhibited the BK-induced inward current in gramicidin-perforated whole-cell patch-clamp recordings of capsaicin-sensitive jugular ganglion neurones retrogradely labelled from the airways. NFA did not inhibit the BK-induced increase in intracellular free Ca2+. The TRPV1 inhibitor, iodo-resiniferatoxin (1 μM), also partially inhibited BK-induced action potential discharge, and the combination of iodo-resiniferatoxin and NFA virtually abolished the BK-induced action potential discharge. We concluded that in vagal afferent C-fibres, BK evokes membrane depolarization and action potential discharge through the additive effects of TRPV1 and Cl- channel activation.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalJournal of Physiology
Volume566
Issue number1
DOIs
StatePublished - Jul 1 2005

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Unmyelinated Nerve Fibers
Chloride Channels
Bradykinin
Guinea Pigs
Action Potentials
Capsaicin
Bronchi
Trachea
Niflumic Acid
Gramicidin
Citric Acid
Ganglia
Membrane Potentials
Chlorides
Neck
Ions
Neurons
Membranes

ASJC Scopus subject areas

  • Physiology

Cite this

Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation. / Lee, Min Goo; Macglashan, Donald; Undem, Bradley J.

In: Journal of Physiology, Vol. 566, No. 1, 01.07.2005, p. 205-212.

Research output: Contribution to journalArticle

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