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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/L898    most recent 00461.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, B. Articles by Hall, I. P. Search for Related Content PubMed PubMed Citation Articles by Liu, B. Articles by Hall, I. P.

Bradykinin activates calcium-dependent potassium channels in cultured human airway smooth muscle cells

Division of Therapeutics and Molecular Medicine, University of Nottingham, Queens Medical Centre, Nottingham, United Kingdom

Submitted 2 November 2005 ; accepted in final form 1 December 2006

Bradykinin (BK) is an inflammatory mediator that can cause bronchoconstriction. In this study, we investigated the membrane currents induced by BK in cultured human airway smooth muscle (ASM) cells. Depolarization of the cells induced outward currents, which were inhibited by tetraethylammonium (TEA) in a concentration-dependent manner with an IC₅₀ of 0.33 µM. The currents were increased by elevating intracellular free Ca²⁺ concentration, suggesting they are calcium-activated potassium channels [I_K(Ca)]. Preexposure to inhibitor of I_K(Ca) of large conductance (BKCa), iberiotoxin, and small conductance (SKCa), apamin, inhibited the increase of outward current induced by BK. The relative contribution of BKCa was greatest in early passage cells. Both nickel and SKF-96365 (10 µM) inhibited the increase of the I_K(Ca) induced by BK; however, the L-type Ca²⁺ channel blocker, nifedipine, had no effect. Activation of the BK-induced current was inhibited by heparin, indicating dependence on intact inositol 1,4,5-triphosphate (IP₃)-sensitive intracellular Ca²⁺ stores. BK also increased inositol phosphate accumulation and induced a transient Ca²⁺-activated chloride current (CACC) and a sustained nonselective cation current (I_CAT). In summary, BK activates BKCa, SKCa, CACC, and I_CAT via IP₃-sensitive stores in human ASM.

asthma; airway tone; bronchial relaxation

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