Fink H S, Maak S, von Lengerken G, Till U
Institute of Pathological Biochemistry, Medical Academy Erfurt, Germany.
Cell Calcium. 1992 Mar;13(3):157-62. doi: 10.1016/0143-4160(92)90043-r.
Since 1966 the domestic pig has served as the animal model in Malignant Hyperthermia (MH) research [1]. The use of genetically well-defined pigs rendered it possible to test the method for diagnosing MH-susceptibility of patients presented in the preceding paper. Thus, the effect of halothane on intracellular calcium movements was studied in Quin-2- and chlorotetracycline-loaded pig platelets. In 'Ca(2+)-free' suspensions the resting level of free cytosolic Ca2+ was about 60 nM. In contrast to the results with human platelets there were no significant differences between pig genotypes either in the absence or in the presence of external calcium. After addition of halothane, a mobilization of intracellular membrane-bound calcium can be observed. However, the calcium mobilization is not accompanied by a marked increase in fluorescence intensity of Quin-2-loaded platelets. Thus, in the absence of external calcium, halothane produces only a slight increase in free cytosolic Ca2+. Nevertheless, the calcium rises measured in platelets from affected animals were statistically significantly higher than those from normal subjects. However, in the presence of 1 mM external calcium, a rapid increase in free cytosolic calcium can be detected after halothane addition. This suggests that halothane causes a marked, dose-dependent increase in Ca2+ permeability of the plasma membrane. Compared to the control group, significantly enhanced calcium permeability was found, not only in homozygous positive pigs, but also in heterozygous animals.
自1966年以来，家猪一直作为恶性高热（MH）研究的动物模型[1]。使用基因明确的猪使得测试前一篇论文中提出的诊断患者MH易感性的方法成为可能。因此，在装载了喹啉-2和氯四环素的猪血小板中研究了氟烷对细胞内钙运动的影响。在“无钙”悬浮液中，游离胞质Ca2+的静息水平约为60 nM。与人类血小板的结果相反，无论有无细胞外钙，猪的不同基因型之间均无显著差异。加入氟烷后，可以观察到细胞内膜结合钙的动员。然而，钙动员并未伴随着装载喹啉-2的血小板荧光强度的显著增加。因此，在没有细胞外钙的情况下，氟烷仅使游离胞质Ca2+略有增加。尽管如此，在患病动物的血小板中测得的钙升高在统计学上显著高于正常动物。然而，在存在1 mM细胞外钙的情况下，加入氟烷后可检测到游离胞质钙迅速增加。这表明氟烷导致质膜Ca2+通透性显著增加，且呈剂量依赖性。与对照组相比，不仅在纯合阳性猪中，而且在杂合动物中均发现钙通透性显著增强。
