BACKGROUND Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on diaphragm muscle during postnatal maturation remain unknown. METHODS The effects of dantrolene (10(-8) to 10(-4) M) were investigated in vitro on diaphragm muscle strips in adult rats and in postnatal rats aged 3, 10, and 17 days, and compared with those of ryanodine (10(-8) to 10(-...

Background Malignant Hyperthermia is a life-threatening condition triggered by exposure to certain general anaesthetics (halothane, sevoflurane, and desflurane) and depolarising muscle relaxants (suxamethonium). Malignant hyperthermia happens primarily due to mutation of the ryanodine receptor type 1 (RYR1), located on the sarcoplasmic reticulum in myocytes. This mutation leads to increase in c...

Effects of dantrolene, a blocker of intracellular Ca2+ release, on the oscillation of the intracellular Ca2+ ([Ca2+]i) induced by caffeine were studied in bullfrog sympathetic ganglion cells, using a Fura-2 fluorescence technique. Dantrolene blocked the Ca2+ oscillation only in the cell illuminated by ultraviolet light (335-385 nm). Likewise, the blocking effects on rhythmic Ca(2+)-dependent hy...

Dantrolene was recently identified as a novel inhibitor of the plasmodial surface anion channel (PSAC), an unusual ion channel on Plasmodium falciparum-infected human red blood cells. Because dantrolene is used clinically, has a high therapeutic index, and has desirable chemical synthetic properties, it may be a lead compound for antimalarial development. However, dantrolene derivatives would n...

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...

1306 June 2014 M hyperthermia (MH) occurs when a patient who has inherited a causative mutation (usually in RYR1, the gene on chromosome 19 that encodes for the ryanodine receptor) is exposed to one or both anesthetic-triggering agents (i.e., volatile anesthetics and succinylcholine).1 MH is just as likely to occur in a healthy patient who receives anesthesia in a freestanding ambulatory surger...

BACKGROUND Malignant hyperthermia (MH) is a rare hypermetabolic syndrome of the skeletal muscle and a potentially fatal complication of general anesthesia. Dantrolene is currently the only specific treatment for MH. The Malignant Hyperthermia Association of the United States has issued guidelines recommending that 36 vials (20 mg per vial) of dantrolene remain in stock at every surgery center. ...

In heart failure (HF), arrhythmogenic Ca(2+) release and chronic Ca(2+) depletion of the sarcoplasmic reticulum (SR) arise due to altered function of the ryanodine receptor (RyR) SR Ca(2+)-release channel. Dantrolene, a therapeutic agent used to treat malignant hyperthermia associated with mutations of the skeletal muscle type 1 RyR (RyR1), has recently been suggested to have effects on the car...

Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthe...

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...