Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation.
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 microM) 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 microM), 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 microM). 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 microM), 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.
Lee
Min-Goo
MG
Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Macglashan
Donald W
DW
Undem
Bradley J
BJ
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D012137:Respiratory System / Q000294:innervation; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D018118:Chloride Channels; D001920:Bradykinin; D002118:Calcium