H(2)O(2) and ethanol act synergistically to gate ryanodine receptor/calcium-release channel.

doi:10.1152/AJPCELL.2000.279.5.C1366

Paper

H(2)O(2) and ethanol act synergistically to gate ryanodine receptor/calcium-release channel.

Published Nov 1, 2000 · Toshiharu Oba, Tatsuya Ishikawa, Takashi Murayama

American journal of physiology. Cell physiology

UNKNOWN SJR score

24

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1

Influential Citations

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Abstract

We examined the effect of low concentrations of H(2)O(2) on the Ca(2+)-release channel/ryanodine receptor (RyR) to determine if H(2)O(2) plays a physiological role in skeletal muscle function. Sarcoplasmic reticulum vesicles from frog skeletal muscle and type 1 RyRs (RyR1) purified from rabbit skeletal muscle were incorporated into lipid bilayers. Channel activity of the frog RyR was not affected by application of 4.4 mM (0.02%) ethanol. Open probability (P(o)) of such ethanol-treated RyR channels was markedly increased on subsequent addition of 10 microM H(2)O(2). Increase of H(2)O(2) to 100 microM caused a further increase in channel activity. Application of 4.4 mM ethanol to 10 microM H(2)O(2)-treated RyRs activated channel activity. Exposure to 10 or 100 microM H(2)O(2) alone, however, failed to increase P(o). Synergistic action of ethanol and H(2)O(2) was also observed on the purified RyR1 channel, which was free from FK506 binding protein (FKBP12). H(2)O(2) at 100-500 microM had no effect on purified channel activity. Application of FKBP12 to the purified RyR1 drastically decreased channel activity but did not alter the effects of ethanol and H(2)O(2). These results suggest that H(2)O(2) may play a pathophysiological, but probably not a physiological, role by directly acting on skeletal muscle RyRs in the presence of ethanol.

In Vitro Study

Study Snapshot

H(2)O(2) and ethanol synergistically activate skeletal muscle ryanodine receptors, suggesting a pathophysiological role for H(2)O(2) in muscle function.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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H(2)O(2) and ethanol act synergistically to gate ryanodine receptor/calcium-release channel.

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References

Citations

Alcohol Use Disorders and Their Harmful Effects on the Contractility of Skeletal, Cardiac and Smooth Muscles

Alcohol misuse negatively affects muscle contraction, affecting various molecular players, and understanding these molecular players could help design pharmacotherapeutics to prevent, ameliorate, or reverse these negative effects.

Centrally formed acetaldehyde mediates ethanol-induced brain PKA activation

Ethanol-induced brain PKA activation is mediated by centrally formed acetaldehyde, and blocking this pathway with -lipoic acid, aminotriazole, and d-penicillamine effectively blocks these effects in mice.

Type 2 ryanodine receptors are highly sensitive to alcohol

Ethanol inhibits type 2 ryanodine receptors (RyR2), leading to constricting of cerebral arteries in rats and humans, by directly targeting and stabilizing their closed states.

Dantrolene blockade of ryanodine receptor impairs ethanol-induced behavioral stimulation, ethanol intake and loss of righting reflex

Dantrolene, a ryanodine receptor antagonist, selectively reduces ethanol-induced behavioral stimulation, loss of righting reflex, and ethanol intake in a dose-dependent manner.

Exercise-induced oxidative stress in humans: cause and consequences.

Prolonged or high-intensity exercise leads to oxidative damage to macromolecules in both blood and skeletal muscle, with the primary site of production still unclear.