Malignant hyperthermia: a pharmacogenetic disorder.
Malignant hyperthermia (MH) is a pharmacogenetic disorder triggered by volatile anesthetics or depolarizing muscle relaxants in predisposed individuals. Exercise or stress-induced MH episodes, in the absence of any obvious pharmacological trigger, have been reported, but these are rare. A considerable effort has taken place over the last two decades to identify mutations associated with MH and characterize their functional effects. A number of different, but complementary systems, have been developed and implemented to this end. The results of such studies have identified commonalities in functional affects of mutations, and also uncovered unexpected complexities in both the structure and function of the skeletal muscle calcium-release channel. The following review is an attempt to provide a summary of the background to current MH research, and highlight some recent advances in our knowledge of the molecular basis of the phenotypic expression of this disorder.
Stowell
Kathryn M
KM
Institute of Molecular Biosciences, Massey University, Palmerston North, New Zealand. k.m.stowell@massey.ac.nz
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D008305:Malignant Hyperthermia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D009125:Muscle Relaxants, Central / Q000009:adverse effects; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010597:Pharmacogenetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics
D009125:Muscle Relaxants, Central; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium