Dantrolene Inhibition of RyR2 requires Calmodulin

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Essential Role of Calmodulin in RyR Inhibition by Dantrolene.

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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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Dantrolene requires Mg2+ to arrest malignant hyperthermia.

Malignant hyperthermia (MH) is a clinical syndrome of skeletal muscle that presents as a hypermetabolic response to volatile anesthetic gases, where susceptible persons may develop lethally high body temperatures. Genetic predisposition mainly arises from mutations on the skeletal muscle ryanodine receptor (RyR). Dantrolene is administered to alleviate MH symptoms, but its mechanism of action a...

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Malignant hyperthermia (MH) is a pharmacogenetic disorder most often linked to mutations in the type 1 ryanodine receptor (RyR1) or the skeletal L-type Ca(2+) channel (Ca(V)1.1). The only effective treatment for an MH crisis is administration of the hydantoin derivative Dantrolene. In addition to reducing voltage induced Ca(2+) release from the sarcoplasmic reticulum, Dantrolene was recently fo...

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ژورنال

عنوان ژورنال: Biophysical Journal

سال: 2015

ISSN: 0006-3495

DOI: 10.1016/j.bpj.2014.11.3194