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

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.