Porcine Malignant Hyperthermia:: Effects of Halothane on Mitochondrial Respiration and Calcium Accumulation
Porcine Malignant Hyperthermia:: Effects of Halothane on Mitochondrial Respiration and Calcium Accumulation
复制标题
猪恶性高热：氟烷对线粒体呼吸和钙积累的影响
作者：
B. Britt;L. Endrenyi;D. Cadman;H. Fan;H. Y. Fung
取正常猪股外侧肌和恶性高温易感猪股外侧肌。麻醉由安定、N_2O：O_2和利多卡因野阻滞组成。易感(MHS)猪肌肉线粒体呼吸控制正常，电子传递加快。谷氨酸对数值Q3‘S和对数值Q4’S与猪体重呈负相关。在谷氨酸存在下，MHS的状态3呼吸是正常线粒体的3.5倍，状态4呼吸是正常线粒体的3.2倍(与重量或氟烷剂量无关)。因此，MHS线粒体能够比正常线粒体更有效地产生ATP。在体外，氟烷抑制谷氨酸Q3‘S和R.C.I.S，略升高琥珀酸Q3’S和R.C.I.S，对谷氨酸或琥珀酸Q4‘S无显著影响，适度降低谷氨酸和琥珀酸P/O比值。这些变化与正常猪相似。MHS线粒体钙摄取明显低于正常，但体外氟烷对线粒体钙摄取无明显改变。这些结果提示，线粒体膜成分是猪恶性高热缺陷的原因，因为钙通常与磷脂晶格的形成有关。
Vastus lateralis muscle was excised from normal pigs and from pigs susceptible to malignant hyperthermia. Anesthesia consisted of diazepam, N2O:O2 and a lidocaine field block. In the susceptible (MHS) pigs, respiratory control in mitochondria of excised muscle was normal, while electron transport was accelerated. Glutamate log Q3's and log Q4's were in inverse linear relationship to porcine weights. In the presence of glutamate, state 3 respiration was 3.5 times, and state 4 respiration 3.2 times, higher in MHS than in normal mitochondria (independent of weight or halothane dose). Thus, the MHS mitochondria were able to produce ATP more efficiently than normal mitochondria. In vitro, halothane inhibited glutamate Q3's and R.C.I.'s, slightly increased succinate Q3's and R.C.I.'s, had no significant effect on glutamate or succinate Q4's, and moderately lowered glutamate and succinate P/O ratios. These changes were similar to those observed in normal pigs. Calcium uptake into MHS mitochondria was markedly less than normal but was not significantly altered by in-vitro halothane. These results suggest a mitochondrial membrane component for the defect of porcine malignant hyperthermia, since calcium is normally associated with the formation of the phospholiptd lattice of this membrane.