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 respo nse to stress and exposure to volatile anaesthetics (halothane, enflur ane) and muscle relaxants. To date, eight point mutations in the ryano dine receptor gene, the Ca2+ release channel of the skeletal muscle sa rcoplasmic reticulum, segregate with the MH phenotype, yet direct evid ence linking altered [Ca2+](i) homeostasis to mutation in recombinant RYR has been obtained only for one such mutation. Most of these mutati ons appear in an ''MH domain'' that is localized at the NH2 terminus o f 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) 1 997, Elsevier Science Inc.