Calcium uptake by isolated sarcoplasmic reticulum: examination of halothane inhibition, pH dependence, and Ca2+ dependence of normal and malignant hyperthermic human muscle

Abstract

Ca2+ uptake and release in muscle homogenates and fragmented sarcoplasmic reticulum were examined in biopsy specimens from nonsusceptible and malignant hyperthermia (MH) susceptible patients. Ca2+ flux was examined by the filter binding assay technique using 45Ca. It was found that Ca2+ uptake and release were the same in both normal and MH muscle homogenates. Halothane inhibited the uptake of Ca2+ by the sarcoplasmic reticulum. The halothane inhibition of Ca2+ uptake in normal and MH sarcoplasmic reticulum was fitted to a single line with a correlation coefficient (r) of -0.958. The pH and Ca2+ dependence of Ca2+ uptake were the same for both normal and MH sarcoplasmic reticulum. The pK for Ca2+ uptake is approximately 5.9. It is concluded that the Ca2+ uptake function of the muscle from the five patients with MH examined is not abnormal and might not be the locus for the initiation of MH.