Essential Role of Calmodulin in RyR Inhibition by Dantrolene

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Essential Role of Calmodulin in RyR Inhibition by Dantrolene s

Dantrolene is the first line therapy of malignant hyperthermia. Animal studies suggest that dantrolene also protects against heart failure and arrhythmias caused by spontaneous Ca release. Although dantrolene inhibits Ca release from the sarcoplasmic reticulum of skeletal and cardiac muscle preparations, its mechanism of action has remained controversial, because dantrolene does not inhibit sin...

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Essential Role of Calmodulin in RyR Inhibition by Dantrolene.

Dantrolene is the first line therapy of malignant hyperthermia. Animal studies suggest that dantrolene also protects against heart failure and arrhythmias caused by spontaneous Ca(2+) release. Although dantrolene inhibits Ca(2+) release from the sarcoplasmic reticulum of skeletal and cardiac muscle preparations, its mechanism of action has remained controversial, because dantrolene does not inh...

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Oxidation of ryanodine receptor (RyR) and calmodulin enhance Ca release and pathologically alter, RyR structure and calmodulin affinity.

Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in heart failure (HF) and arrhythmias. Altered RyR2 domain-domain interaction (domain unzipping) and calmodulin (CaM) binding affinity are allosterically coupled indices of RyR2 conformation. In HF RyR2 exhibits reduced CaM binding, increased domain unzipping and greater SR Ca leak, and dantrolene can reverse these...

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spectroscopic studies of inhibition of calmodulin activity by some drugs

the effect of four inhibitors on calmalulin (cum) were studied by a ftuorescence and ultraviolet techniques. four compounds in - ( 6 - aminohexyt) 5-chloro - i - napthalenesulphonamide] (w-7), 1 - [ bis - (4 - chtorophenyt) methyl] - 3 - [2, 4-dichloro - β - ( 2 , 4 - dichlorobenzyloxyl) phenethyt] imidazolium chloride (r24571), trifluoperazine (tfp) , thiodiphenylamide chloride (tdpac) showed ...

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The inhibition of acetylcholinesterase by dantrolene and ondansetron.

PURPOSE A virtual screening study has suggested that the skeletal muscle relaxant, dantrolene, and the antiemetic drug, ondansetron, may act as inhibitors of the enzyme acetylcholinesterase (AChE). Based on this proposal, the current study examines the AChE inhibitory properties of these drugs. METHODS AND FINDINGS Using AChE from human erythrocytes as enzyme source, it is shown that dantrole...

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ژورنال

عنوان ژورنال: Molecular Pharmacology

سال: 2015

ISSN: 0026-895X,1521-0111

DOI: 10.1124/mol.115.097691