Malignant hyperthermia domain in the regulation of Ca2+ release channel (ryanodine receptor)

Malignant hyperthermia (MH) is a potentially lethal condition that is manifested in humans as an acute increase of body temperature in response to stress and exposure to volatile anaesthetics (halothane, enflurane) and muscle relaxants. To date, eight point mutations in the ryanodine receptor gene, the Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, segregate with the MH phenotype, yet direct evidence linking altered [Ca2+](i) homeostasis to mutation in recombinant RYR has been obtained only for one such mutation. Most of these mutations appear in an ''MH domain'' that is localized at the NH2 terminus of the skeletal muscle ryanodine receptor Ca2+ channel. In this review, we summarize the available data concerning the role of the MH domain in the altered functions of the ryanodine receptor Ca2+ channel. (C) 1997, Elsevier Science Inc.