Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant inherited arrhythmogenic disorder. Type 1 CPVT (CPVT1) is caused by cardiac ryanodine receptor (RyR2) gene mutations resulting in abnormal calcium release from sarcoplasmic reticulum. Dantrolene, an inhibitor of sarcoplasmic Ca(2+) release, has been shown to rescue this abnormal Ca(2+) release in vitro. We assess...

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...

UNLABELLED Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. We tested the hypothesis that dantrolene reduces the threshold (triggering core temperature) and gain (incremental increase) of shivering. Healthy volunteers were evaluated on 2 random days: control and dantrolene (approximately 2.5 mg/kg plus a continuous infusion). In St...

Oral dantrolene causes a dose-dependent depression of skeletal muscle contractility. A 52-year-old man treated with oral dantrolene for spasticity after spinal cord injury was scheduled to undergo irrigation and drainage of a thigh abscess under general anesthesia. He had taken 50 mg oral dantrolene per day for 3 years. Under standard neuromuscular monitoring, anesthesia was performed with prop...

BACKGROUND Excessive extracellular glutamate produced by cerebral ischemia has been proposed to initiate the cascade toward neuronal cell death. Changes in extracellular glutamate concentration are closely linked to changes in intracellular calcium ion concentration. Dantrolene inhibits calcium release from intracellular calcium stores. In this study, the authors investigated the effects of dan...

In our study, effects of dantrolene sodium on glucose 6-phosphate dehydrogenase (G6PD) were examined in the human erythrocytes in vitro and in rat erythrocytes in vivo. Human erythrocyte G6PD was purified using ammonium sulfate fractionation and 2',5'-ADP Sepharose 4B affinity chromatography. The enzyme activity was determined by Beutler's method. The overall purification procedures gave the hu...

Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on the myopathic diaphragm remain unknown. The effects of dantrolene 10(-8) to 10(-4) mol litre-1 on diaphragm muscle strips in normal (n = 12) and myopathic hamsters (n = 13) were investigated in vitro in response to tetanic stimulation. We studied contraction under isotonic and isometric conditio...

Domeier TL, Roberts CJ, Gibson AK, Hanft LM, McDonald KS, Segal SS. Dantrolene suppresses spontaneous Ca release without altering excitation-contraction coupling in cardiomyocytes of aged mice. Am J Physiol Heart Circ Physiol 307: H818–H829, 2014. First published July 18, 2014; doi:10.1152/ajpheart.00287.2014.—Cardiac dysfunction in the aged heart reflects abnormalities in cardiomyocyte Ca home...

1 A combination of electrical and pharmacological stimulation has been used to compare the effects of sodium thiocyanate and dantrolene sodium on the excitation-contraction coupling (ECC) mechanism of the mouse soleus muscle. 2 Thiocyanate prolonged the 'active state' after electrical stimulation and increased the response to 8 mM caffeine and 80 mM KCl. Dantrolene had an opposite effect to thi...