Role of 20-HETE in the hypoxia-induced activation of Ca2+-activated K+ channel currents in rat cerebral arterial muscle cells

• Published in: American journal of physiology. Heart and circulatory physiology 2008-01, Vol.294 (1), p.H107-H120
• Main Authors: Gebremedhin, Debebe, Yamaura, Ken, Harder, David R
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Calcium - metabolism; Cell Hypoxia; Cerebral Arteries - metabolism; Chromatography, High Pressure Liquid; Cyclic N-Oxides - pharmacology; Cytochrome P-450 CYP4A - antagonists & inhibitors; Cytochrome P-450 CYP4A - metabolism; Enzyme Inhibitors - pharmacology; Fatty Acids, Unsaturated - pharmacology; Hydroxyeicosatetraenoic Acids - metabolism; Hydroxylation; In Vitro Techniques; Ion Channel Gating; Male; Mass Spectrometry; Membrane Potentials; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - enzymology; Myocytes, Smooth Muscle - metabolism; Patch-Clamp Techniques; Peptides - pharmacology; Potassium - metabolism; Potassium Channel Blockers - pharmacology; Potassium Channels, Calcium-Activated - antagonists & inhibitors; Potassium Channels, Calcium-Activated - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Spectrometry, Fluorescence; Spin Labels; Superoxides - metabolism; Tetraethylammonium - pharmacology; Vasodilation - drug effects
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01416.2006

1 Department of Physiology and 2 Cardiovascular Research Center, Medical College of Wisconsin, and 3 Clement Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin Submitted 26 December 2006 ; accepted in final form 28 September 2007 The mechanism of sensing hypoxia and hypoxia-induced activation of cerebral arterial Ca 2+ -activated K + (K Ca ) channel currents and vasodilation is not known. We investigated the roles of the cytochrome P -450 4A (CYP 4A) -hydroxylase metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), and generation of superoxide in the hypoxia-evoked activation of the K Ca channel current in rat cerebral arterial muscle cells (CAMCs) and cerebral vasodilation. Patch-clamp analysis of K + channel current identified a voltage- and Ca 2+ -dependent 238 ± 21-pS unitary K + currents that are inhibitable by tetraethylammonium (TEA, 1 mM) or iberiotoxin (100 nM). Hypoxia (