Development of a diagnostic method for malignant hyperthermia indexed by cell death provoked by stimulation of ryanodine 1 receptors in monocytes

为了开发一种新的恶性高热诊断方法，评估单核细胞RyR1受体激动剂引起的坏死细胞毒性试验的实用性。两种RyR1激动剂，布比卡因和咖啡因，升高了细胞内Ca^2+浓度。然而，布比卡因而不是咖啡因引起细胞死亡。这些RyR1激动剂对线粒体膜电位的不同影响模仿了坏死细胞死亡的影响。这表明细胞内Ca^2+动员不是RyR1激动剂引起细胞死亡的直接原因。应进一步评价RyR1激动剂引起的线粒体损伤和坏死之间的关系。

To develop a new diagnostic method for malignant hyperthermia, utility of necrotic cytotoxicity assay provoked by agonists for ryanodine-1 receptors(RyR1) in monocytes was evaluated. Two RyR1 agonists, bupivacaine as well as caffeine, elevated intracellular Ca^<2+> concentration. However, bupivacaine but not caffeine provoked cell death. Differential effects of these RyR1 agonists on mitochondrial membrane potential mimicked those on necrotic cell death. These indicated that intracellular Ca^<2+> mobilization was not the direct cause of cell death provoked by RyR1 agonists. Further evaluation concerning the relationship between mitochondrial damage and necrosis provoked by RyR1 agonists should be required.