Overexcited MaxiK and KATP channels underlie obstructive jaundice-induced vasoconstrictor hyporeactivity of arterial smooth muscle

• Published in: Scientific reports Vol. 6; no. 1; p. 39246
• Main Authors: Yuan, Ya-wei, Wang, Long, Lu, Zhan-ying, Long, Yue, Jiao, Ying-fu, Xia, Qiang, Wen, Da-xiang, Yu, Wei-feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.12.2016; Nature Publishing Group
• Subjects: 13/51; 631/57/2270; 631/80/304; 82; 82/80; 9/74; Aorta; Bile; Bile ducts; Charybdotoxin; Cholestasis; Contraction; Denudation; Glibenclamide; Humanities and Social Sciences; Jaundice; multidisciplinary; Norepinephrine; Potassium channels; Potassium channels (inwardly-rectifying); Rodents; Science; Smooth muscle; Studies; Thorax
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep39246

Substantial evidence has shown that obstructive jaundice can induce vascular hyporesponsiveness. The present study was designed to investigate mechanisms of MaxiK channel and K ATP underlying cholestasis-induced vascular dysfunction. The isolated thoracic aorta was used to explore norepinephrine (NE)-induced contraction. The function of MaxiK and K ATP channels 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 K ATP current 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 K ATP channels play an important role in regulating vascular hyporesponsiveness in BDL rats.