Iaizzo P A, Seewald M J, Olsen R, Wedel D J, Chapman D E, Berggren M, Eichinger H M, Powis G
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
Anesthesiology. 1991 Mar;74(3):531-8. doi: 10.1097/00000542-199103000-00023.
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.
氟烷以剂量依赖的方式诱导从猪制备的肝细胞中细胞内Ca2+的释放。氟烷诱导的释放幅度对于从易患恶性高热（MH）的动物制备的肝细胞比对于从正常猪制备的肝细胞更大。使用两种不同的方法来确定氟烷诱导的Ca2+释放：1）测量从皂素通透的肝细胞的非线粒体储存中45Ca2+的释放；2）记录加载有Ca2+敏感光蛋白水母发光蛋白的完整肝细胞的发光变化。还观察到，虽然1,4,5-肌醇三磷酸（IP3）、鸟苷-5-三磷酸和花生四烯酸都诱导从通透的猪肝细胞中显著释放45Ca2+，但对于从易患MH的动物制备的肝细胞，只有IP3释放的45Ca2+量显著更大。这些数据表明从易患MH的猪分离的肝细胞中存在异常的Ca2+稳态，这支持了多器官的膜系统可能在这种遗传性疾病中受到影响的假设。
