Department of Anaesthesiology, Ulm University, Ulm, Germany.
Acta Anaesthesiol Scand. 2013 Sep;57(8):1017-23. doi: 10.1111/aas.12126. Epub 2013 May 3.
A common form of congenital myotonia, myotonia congenita (MC), is caused by mutations in the skeletal muscle Cl(-) channel gene type 1 (CLCN1). Due to the reduced Cl(-) conductance of the mutated channels, the patients may develop generalized muscle rigidity and hypermetabolism during general anaesthesia. The clinical symptoms resemble malignant hyperthermia (MH), which may lead to mistreatment of the patient.
Muscle specimens of ADR mice (an animal model of MC) as well as of human individuals were used and exposed to potent ryanodine receptor type 1 (RyR1) activators and increasing K(+) concentration. Muscle force was monitored by a standardized diagnostic method for MH, the so-called in vitro contracture test.
Neither muscle of ADR mice nor MC muscle (murine and human myotonic muscle) showed pathological contractures after exposure to the potent RyR1 agonists caffeine and halothane. Increasing concentrations of K(+) had a dose-dependent preventive effect on myotonic stiffness.
We conclude that the adverse anaesthetic MH-like episodes observed in MC patients do not primarily originate from an altered Ca(2+) release in skeletal muscle. In MC muscle, this hypermetabolism is facilitated by a (pharmacologically induced) sustained depolarization due to an instable membrane potential. The in vitro results suggest that these patients benefit from tight K(+) monitoring because of the membrane potential stabilizing effect of K(+) .
先天性肌强直（MC）是一种常见的先天性肌病，由骨骼肌氯离子通道基因 1 型（CLCN1）的突变引起。由于突变通道的氯离子电导降低，患者在全身麻醉期间可能会出现全身肌肉僵硬和代谢亢进。其临床症状类似于恶性高热（MH），这可能导致对患者的误治。
使用 ADR 小鼠（MC 的动物模型）以及人类个体的肌肉标本，并暴露于强效肌质网钙释放通道 1 型（RyR1）激活剂和增加的 K+浓度下。通过一种称为体外挛缩试验的 MH 标准诊断方法监测肌肉力。
ADR 小鼠的肌肉以及 MC 肌肉（鼠和人类肌强直肌肉）在暴露于强效 RyR1 激动剂咖啡因和氟烷后均未出现病理性挛缩。增加 K+浓度对肌强直僵硬具有剂量依赖性的预防作用。
我们的结论是，在 MC 患者中观察到的不良麻醉似 MH 发作并非主要源自骨骼肌中 Ca2+释放的改变。在 MC 肌肉中，由于膜电位不稳定导致持续去极化，这种代谢亢进得到促进。体外结果表明，这些患者受益于紧密的 K+监测，因为 K+具有稳定膜电位的作用。
