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First published online on April 28, 2005.
Copyright © 2005 by The Physiological Society
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Received March 28, 2005
Revised April 22, 2005
Accepted after revision April 22, 2005

"Role of Chloride Channels in Bradykinin-Induced Guinea Pig Airway Vagal C-fiber Activation"

Min-Goo Lee1, Donald MacGlashan Jr.1, and Bradley J. Undem1*

1 Johns Hopkins University

* To whom correspondence should be addressed. E-mail: bundem{at}jhmi.edu.

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-fibers. In an ex vivo innervated trachea/bronchus preparation, BK (1 µM) consistently produced action potential discharge in vagal afferent C-fibers with receptive fields in the trachea or main stem bronchus. The calcium-activated chloride 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-fibers. 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 neurons retrogradely labeled from the airways. NFA did not inhibit the BK-induced increase in intracellular free calcium. 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-fibers, BK evokes membrane depolarization and action potential discharge through the additive effects of TRPV1 and chloride channel activation.


Key words: Bradykinin • C fibre • Chloride channel




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