Determinates of Dantrolene Inhibition of Ryanodine Receptors

Dantrolene Inhibition of Sarcoplasmic Reticulum Ca Release by Direct and Specific Action at Skeletal Muscle Ryanodine Receptors*

The skeletal muscle relaxant dantrolene inhibits the release of Ca from the sarcoplasmic reticulum during excitation-contraction coupling and suppresses the uncontrolled Ca release that underlies the skeletal muscle pharmacogenetic disorder malignant hyperthermia; however, the molecular mechanism by which dantrolene selectively affects skeletal muscle Ca regulation remains to be defined. Here w...

Dantrolene inhibition of sarcoplasmic reticulum Ca2+ release by direct and specific action at skeletal muscle ryanodine receptors.

The skeletal muscle relaxant dantrolene inhibits the release of Ca2+ from the sarcoplasmic reticulum during excitation-contraction coupling and suppresses the uncontrolled Ca2+ release that underlies the skeletal muscle pharmacogenetic disorder malignant hyperthermia; however, the molecular mechanism by which dantrolene selectively affects skeletal muscle Ca2+ regulation remains to be defined. ...

Dantrolene inhibition of ryanodine receptor Ca2+ release channels. Molecular mechanism and isoform selectivity.

As an inhibitor of Ca(2+) release through ryanodine receptor (RYR) channels, the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca(2+) signaling and a lifesaving treatment for the pharmacogenetic disorder malignant hyperthermia. However, the molecular basis and specificity of the actions of dantrolene on RYR channels have remained in que...

Dantrolene inhibition of ryanodine receptor Ca release channels: molecular mechanism and isoform selectivity

Dantrolene rescues aberrant N-terminus intersubunit interactions in mutant pro-arrhythmic cardiac ryanodine receptors.

AIMS The ryanodine receptor (RyR2) is an intracellular Ca(2+) release channel essential for cardiac excitation-contraction coupling. Abnormal RyR2 channel function results in the generation of arrhythmias and sudden cardiac death. The present study was undertaken to investigate the mechanistic basis of RyR2 dysfunction in inherited arrhythmogenic cardiac disease. METHODS AND RESULTS We presen...