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Type 2 ryanodine receptors are highly sensitive to alcohol
Author(s) -
Ye Yanping,
Jian Kuihuan,
Jaggar Jonathan H.,
Bukiya An.,
Dopico Alex M.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.03.005
Subject(s) - ryanodine receptor , ryanodine receptor 2 , ethanol , chemistry , receptor , alcohol , biophysics , vasodilation , cerebral arteries , microbiology and biotechnology , medicine , endocrinology , biology , biochemistry
Exposure to ethanol levels reached in circulation during alcohol intoxication ( > 10 mM) constricts cerebral arteries in rats and humans. Remarkably, targets and mechanisms underlying this action remain largely unidentified. Artery diameter is regulated by myocyte Ca 2+ 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 Ca 2+ spark and RyR2 activity with IC 50 < 20 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.