Malignant hyperthermia: halothane- and calcium-induced calcium release in skeletal muscle

The temperature dependence of oleic acid-enhanced halothane- induced Ca2+ release and the existence of a reduced threshold of Ca(2+)-induced Ca2+ release were examined to determine their roles in human malignant hyperthermia. Halothane (8-11 mM) induced Ca2+ release from terminal cisternae-containing preparations from skeletal muscle. Oleic acid (15 microM) markedly reduced the threshold of halothane-induced Ca2+ release to < 0.5 mM at 37 degrees C, but not at 25 degrees C, consistent with the temperature dependence of halothane action in intact muscle. Two states of the threshold of Ca(2+)-induced Ca2+ release were unrelated to malignant hyperthermia in humans, in contrast to pigs. Excess fatty acid production may be an important modulator of halothane action in malignant hyperthermia.