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Role of chloride channels in bradykinin‐induced guinea pig airway vagal C‐fibre activation
Author(s) -
Lee MinGoo,
MacGlashan Donald W.,
Undem Bradley J.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.087577
Subject(s) - bradykinin , guinea pig , chemistry , chloride channel , airway , anesthesia , medicine , endocrinology , biochemistry , receptor
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 μ m ) consistently produced action potential discharge in vagal afferent C‐fibres with receptive fields in the trachea or main stem bronchus. The Ca 2+ ‐activated Cl − channel (CLCA) inhibitor, niflumic acid (NFA, 100 μ m ), 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 μ m ). 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 Ca 2+ . The TRPV1 inhibitor, iodo‐resiniferatoxin (1 μ m ), 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.