20-HETE inotropic effects involve the activation of a nonselective cationic current in airway smooth muscle - PubMed (original) (raw)

. 2003 Sep;285(3):L560-8.

doi: 10.1152/ajplung.00381.2002. Epub 2003 May 16.

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• PMID: 12754190
• DOI: 10.1152/ajplung.00381.2002

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20-HETE inotropic effects involve the activation of a nonselective cationic current in airway smooth muscle

Martin Cloutier et al. Am J Physiol Lung Cell Mol Physiol. 2003 Sep.

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Abstract

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 microM. This inotropic response was insensitive to GF-109203X, a PKC inhibitor. The sustained contraction, requiring Ca2+ entry, was partially blocked by either 100 microM Gd3+ or 1 microM nifedipine, revealing the involvement of noncapacitative Ca2+ entry and L-type Ca2+ channels, respectively. Microelectrode measurements showed that 3 microM 20-HETE depolarized the membrane potential in guinea pig ASM by 13 +/- 2mV(n = 7), as did 30 microM 1-oleoyl-2-acetyl-sn-glycerol. Depolarizing effects were also observed in the absence of epithelium. Patch-clamp recordings demonstrated that 1 microM 20-HETE activated a nonselective cationic inward current that may be supported by the activation of transient receptor potential channels. The presence of canonical transient receptor potential mRNA was confirmed by RT-PCR in guinea pig ASM cells.

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