Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10870732 | FEBS Letters | 2014 | 7 Pages |
Abstract
Exposure to ethanol levels reached in circulation during alcohol intoxication (>10Â mM) constricts cerebral arteries in rats and humans. Remarkably, targets and mechanisms underlying this action remain largely unidentified. Artery diameter is regulated by myocyte Ca2+ sparks, a vasodilatory signal contributed to by type 2 ryanodine receptors (RyR2). Using laser confocal microscopy in rat cerebral arteries and bilayer electrophysiology we unveil that ethanol inhibits both Ca2+ spark and RyR2 activity with IC50Â <Â 20Â mM, placing RyR2 among the ion channels that are most sensitive to ethanol. Alcohol directly targets RyR2 and its lipid microenvironment, leading to stabilization of RyR2 closed states.
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Authors
Yanping Ye, Kuihuan Jian, Jonathan H. Jaggar, Anna N. Bukiya, Alex M. Dopico,