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Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
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Type 2 ryanodine receptors are highly sensitive to alcohol
Yanping Ye1, Kuihuan Jian1, Jonathan H Jaggar2
1Department of Pharmacology, The University of Tennessee Health Science Center, Memphis, TN 38163, United States.
FEBS Letters
|March 18, 2014
Summary
Ethanol constricts cerebral arteries by inhibiting calcium (Ca2+) sparks. Researchers found that alcohol directly targets type 2 ryanodine receptors (RyR2), stabilizing their closed state and impacting blood flow.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Pharmacology
Background:
- Ethanol intoxication causes cerebral artery constriction in humans and rats.
- The specific molecular targets and mechanisms responsible for this effect are largely unknown.
- Myocyte Ca(2+) sparks, regulated by type 2 ryanodine receptors (RyR2), are crucial for maintaining cerebral artery diameter.
Purpose of the Study:
- To identify the molecular targets and mechanisms through which ethanol induces cerebral artery constriction.
- To investigate the role of type 2 ryanodine receptors (RyR2) in ethanol-induced cerebral artery dysfunction.
Main Methods:
- Utilized laser confocal microscopy on rat cerebral arteries.
- Employed bilayer electrophysiology to study ion channel activity.
- Quantified the inhibitory effects of ethanol on Ca(2+) sparks and RyR2 activity.
Main Results:
- Ethanol was found to inhibit both Ca(2+) spark and RyR2 activity with an IC50 < 20 mM.
- RyR2 emerged as one of the most ethanol-sensitive ion channels identified.
- Evidence suggests direct interaction of alcohol with RyR2 and its surrounding lipid environment, promoting closed-state stabilization.
Conclusions:
- Type 2 ryanodine receptors (RyR2) are a primary molecular target for ethanol in cerebral arteries.
- Ethanol's inhibition of RyR2 activity and Ca(2+) sparks contributes to cerebral artery constriction.
- Understanding this mechanism provides insight into alcohol's vascular effects.
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