title: Overexcited MaxiK and KATPchannels underlie obstructive jaundice-induced vasoconstrictor hyporeactivity of arterial smooth muscle.
abstract: Substantial evidence has shown that obstructive jaundice can induce vascular hyporesponsiveness. The present study was designed to investigate mechanisms of MaxiK channel and KATPunderlying cholestasis-induced vascular dysfunction. The isolated thoracic aorta was used to explore norepinephrine (NE)-induced contraction. The function of MaxiK and KATPchannels were investigated using whole-cell patch clamp recording. Compared with Sham group, NE-induced vascular contraction was blunted after bile duct ligation (BDL), which could not be ameliorated significantly after endothelial denudation. Charybdotoxin and glibenclamide induced a more pronounced recovery from vascular hyporesponsiveness to NE in BDL group compared with Sham group. BDL significantly promoted the charybdotoxin sensitive MaxiK current and KATPcurrent in isolated aortic smooth muscle cells. In addition, the expression of auxiliary subunits (MaxiK-β1 and SUR2B) rather pore-forming subunits (MaxiK-α and Kir6.1) was significantly up-regulated after BDL. These findings suggest that MaxiK and KATPchannels play an important role in regulating vascular hyporesponsiveness in BDL rats.
authors.affiliation: Department of Anesthesiology, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology and Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Physiology and Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, PR China.
authors.forename: Zhan-Ying
authors.initials: ZY
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology and Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Anesthesiology, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ying-Fu
authors.initials: YF
authors.lastname: Jiao
authors.affiliation: Department of Liver Surgery, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Da-Xiang
authors.initials: DX
authors.lastname: Wen
authors.affiliation: Department of Anesthesiology, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Anesthesiology and Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Yu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001663:Bilirubin / Q000097:blood; D018999:Charybdotoxin / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D041781:Jaundice, Obstructive / Q000378:metabolism / Q000473:pathology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D018999:Charybdotoxin; D001663:Bilirubin; D005905:Glyburide; D009638:Norepinephrine