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

• Published in: Scientific reports 2016-12, Vol.6, 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: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Bilirubin - blood; Charybdotoxin - pharmacology; Glyburide - pharmacology; In Vitro Techniques; Jaundice, Obstructive - metabolism; Jaundice, Obstructive - pathology; KATP Channels - antagonists & inhibitors; KATP Channels - genetics; KATP Channels - metabolism; Large-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors; Large-Conductance Calcium-Activated Potassium Channels - genetics; Large-Conductance Calcium-Activated Potassium Channels - metabolism; Male; Microscopy, Fluorescence; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Norepinephrine - pharmacology; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Up-Regulation
• ISSN: 2045-2322

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