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1 Department of Physiology and Biophysics, University of Sherbrooke, Sherbrooke, QC, Canada
* To whom correspondence should be addressed. E-mail: Eric.Rousseau{at}USherbrooke.ca.
20-hydroxyeicosatetraenoic acid (20-HETE) controls several mechanisms such as vasoactivity, mitogenicity and ion transport in various tissues. Our goal was to quantify the effects of 20-HETE on the electrophysiological properties of airway smooth muscle (ASM). Isometric tension measurements, performed on guinea pig ASM, showed that 20-HETE induced a dose-dependent inotropic effect with an EC50 value of 1.5 µM. This inotropic response was insensitive to GF109203X, a PKC-inhibitor. The sustained contraction, requiring Ca2+ entry, was partially blocked by either 100 µM Gd3+ or 1 µM nifedipine, revealing the involvement of non-capacitative Ca2+ entry and L-type Ca2+ channels, respectively. Microelectrode measurements showed that 3 µM 20-HETE depolarized the membrane potential in guinea pig ASM by 13 ± 2 mV (n = 7), as did 30 µM OAG. Depolarizing effects were also observed in the absence of epithelium. Patch clamp recordings demonstrated that 1 µM 20-HETE activated a non-selective cationic inward current which may be supported by the activation of TRP channels. The presence of TRPC mRNA was confirmed by RT-PCR in guinea pig ASM cell.
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