Azumolene inhibits a component of store-operated calcium entry coupled to the skeletal muscle ryanodine receptor.

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Zhao X, Weisleder N, Han X, Pan Z, Parness J, Brotto M, Ma J

Azumolene inhibits a component of store-operated calcium entry coupled to the skeletal muscle ryanodine receptor.

J Biol Chem. 2006 Nov 3;281(44):33477-86. Epub 2006 Aug 31.

PubMed ID

16945924 [ View in PubMed

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Abstract

Dantrolene reduces the elevated myoplasmic Ca(2+) generated during malignant hyperthermia, a pharmacogenetic crisis triggered by volatile anesthetics. Although specific binding of dantrolene to the type 1 ryanodine receptor (RyR1), the Ca(2+) release channel of skeletal muscle sarcoplasmic reticulum, has been demonstrated, there is little evidence for direct dantrolene inhibition of RyR1 channel function. Recent studies suggest store-operated Ca(2+) entry (SOCE) contributes to skeletal muscle function, but the effect of dantrolene on this pathway has not been examined. Here we show that azumolene, an equipotent dantrolene analog, inhibits a component of SOCE coupled to activation of RyR1 by caffeine and ryanodine, whereas the SOCE component induced by thapsigargin is not affected. Our data suggest that azumolene distinguishes between two mechanisms of cellular signaling to SOCE in skeletal muscle, one that is coupled to and one independent from RyR1.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dantrolene	Ryanodine receptor 1	Protein	Humans	Yes	Antagonist	Details