Mechanism related to docosahexaenoic acid induced large conductance calcium-activated potassium channel currents increase in coronary smooth muscle cells.
- Author:
Ru-xing WANG
1
;
Ku-lin LI
;
Chang-ying ZHANG
;
Jie ZHENG
;
Su-xia GUO
;
Ying WU
;
Xiao-rong LI
;
Qiang CHAI
;
Tong LU
;
Hon-chi LEE
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Coronary Vessels; cytology; drug effects; metabolism; Cytochrome P-450 Enzyme Inhibitors; Docosahexaenoic Acids; pharmacology; Fatty Acids, Unsaturated; pharmacology; Large-Conductance Calcium-Activated Potassium Channels; metabolism; Muscle, Smooth, Vascular; drug effects; metabolism; Myocytes, Smooth Muscle; drug effects; metabolism; Proadifen; pharmacology; Rats; Rats, Sprague-Dawley
- From: Chinese Journal of Cardiology 2011;39(4):348-352
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism of enhanced large conductance calcium-activated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA).
METHODSCoronary SMCs were isolated by enzyme digestion. Potassium channels in coronary SMCs were identified by applications of different potassium blockers. Effects of DHA and its metabolite 16, 17-epoxydocosapentaenoic acid (16, 17-EDP) on BK channels in the absence and presence of cytochrome P450 epoxygenase inhibitor SKF525A were studied by patch clamp in whole-cell configuration.
RESULTSBK channels were widely distributed in SMCs, and BK currents in normal SMCs accounted for (64.2 ± 2.7)% of total potassium currents (n = 20). DHA could activate BK channels, and its 50% effective concentration (EC(50)) was (0.23 ± 0.03) µmol/L, however, the effect of DHA on BK channels was abolished after SMCs were incubated with cytochrome P450 epoxygenase inhibitor SKF525A. 16, 17-EDP, a metabolite of DHA, could reproduce the effects of DHA on BK channels, and its EC(50) was (19.7 ± 2.8) nmol/L.
CONCLUSIONDHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.
