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

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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.