Enhanced mobilization of intracellular Ca²⁺ induced by halothane in hepatocytes isolated from swine susceptible to malignant hyperthermia

Halothane, in a dose-dependent manner, induced the release of intracellular Ca²⁺ in hepatocytes prepared from swine. The magnitude of the release induced by halothane was greater for hepatocytes prepared from animals susceptible to malignant hyperthermia (MH) than for those from normal swine. Two different methods were used to ascertain the release of Ca²⁺ induced by halothane: 1) the release of ⁴⁵Ca²⁺ from nonmitochondrial stores of saponin-permeabilized hepatocytes was measured; and 2) changes in luminescence from intact hepatocytes loaded with the Ca²⁺-sensitive photoprotein aequorin were recorded. It was also observed that, although 1,4,5-inositol trisphosphate (IP₃), guanosine-5-triphosphate, and arachidonic acid all induced a significant release of ⁴⁵Ca²⁺ from permeabilized swine hepatocytes, only the quantities of ⁴⁵Ca²⁺ released by IP₃ were significantly greater for the hepatocytes prepared from the animals susceptible to MH. These data indicate an abnormal Ca²⁺ homeostasis in hepatocytes isolated from swine susceptible to MH, which supports the hypothesis that membrane systems from multiple organs may be affected in this genetic disorder.