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.
Fletcher
J E
JE
Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102-1192.
Tripolitis
L
L
Rosenberg
H
H
Beech
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D006736:Horses; D006801:Humans; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature
D009829:Oleic Acids; D012430:Ruthenium Red; D019301:Oleic Acid; D002118:Calcium; D006221:Halothane