Evidence for Intraluminal Ca Regulatory Site Defect in

Malignant hyperthermia (MH) is a pharmacogenetic disease of humans and various animal species that predisposes to a life-threatening, anesthetic agent-induced syndrome. MH is thought to be a consequence of abnormal, sustained increases in my-oplasmic Ca and sarcoplasmic reticulum (SR) membranes from MH muscle have been shown to have a Ca release channel defect. In the present study we have tested a hypothesis that the abnormal Ca release mechanism in MH can be expressed when Ca is loaded in the presence of pyrophosphate. SR membrane vesicles isolated from normal and MH pig muscle were loaded with Ca in the presence and absence of pyro-phosphate until Ca-induced Ca release occurred. Under both circumstances the threshold amount of Ca loaded until Ca release occurred was lower in the SR from MH pig skeleta