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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/L1037    most recent 00145.2007v1 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 ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Morin, C. Articles by Rousseau, E. Search for Related Content PubMed PubMed Citation Articles by Morin, C. Articles by Rousseau, E.

Functional effects of 20-HETE on human bronchi: hyperpolarization and relaxation due to BK_Ca channel activation

¹Le Bilarium, Department of Physiology and Biophysics, ²Service of Thoracic Surgery, ³Department of Pathology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada

Submitted 12 April 2007 ; accepted in final form 24 July 2007

Airway smooth muscle (ASM) metabolizes arachidonic acid (AA) through various enzymatic pathways, including cytochrome P-450 (CYP-450) -hydroxylase, which leads to the production of 20-hydroxyeicosatetraenoic acid (20-HETE). The goal of this study was to delineate the mode of action of 20-HETE in human ASM cells. Isometric tension measurements demonstrated that 20-HETE induced a concentration-dependent relaxant effect in ASM on bronchi precontracted with either methacholine or AA. Relaxing effects of 20-HETE on resting tone were prevented by 10 nM iberiotoxin (IbTx), a BK_Ca channel inhibitor. Microelectrode measurements showed that exogenous additions of 20-HETE (0.1–10 µM) hyperpolarized the membrane potential of human ASM cells. This concentration-dependent electrophysiological effect induced by the eicosanoid was prevented by 10 nM IbTx. Complementary experiments, using the planar lipid bilayer reconstitution technique, demonstrated that 20-HETE activated reconstituted BK_Ca channels at low free Ca²⁺ concentrations. Together, these results indicate that 20-HETE-dependent activation of BK_Ca channels is responsible for the hyperpolarization and controlled relaxation of ASM in human distal bronchi.

20-hydroxyeicosatetraenoic acid; organ culture; membrane potential

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