title: [Mechanism related to docosahexaenoic acid induced large conductance calcium-activated potassium channel currents increase in coronary smooth muscle cells].
abstract: OBJECTIVE
  To investigate the mechanism of enhanced large conductance calcium-activated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA).
  
  
  METHODS
  Coronary 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.
  
  
  RESULTS
  BK 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.
  
  
  CONCLUSIONS
  DHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.
authors.affiliation: Department of Cardiology, Wuxi People's Hospital Affiliated to Nangjing Medical University, Wuxi 214023, China.
authors.forename: Ru-xing
authors.initials: RX
authors.lastname: Wang
authors.forename: Ku-lin
authors.initials: KL
authors.lastname: Li
authors.forename: Chang-ying
authors.initials: CY
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.forename: Su-xia
authors.initials: SX
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiao-rong
authors.initials: XR
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chai
authors.forename: Tong
authors.initials: T
authors.lastname: Lu
authors.forename: Hon-chi
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D051036:Large-Conductance Calcium-Activated Potassium Channels; D004281:Docosahexaenoic Acids; D011335:Proadifen; C026219:docosapentaenoic acid