Haeseler G, Störmer M, Mohammadi B, Bufler J, Dengler R, Piepenbrock S, Leuwer M
Department of Anesthesiology, OE8050, Hannover Medical School, D-30623 Hannover, Germany. haeseler@
Muscle Nerve. 2001 Jun;24(6):736-43. doi: 10.1002/mus.1064.
We examined the effects of propofol on a paramyotonia congenita mutant skeletal muscle sodium channel in vitro, because life-threatening complications resulting from severe muscle rigidity during induction of anesthesia have been observed using other anesthetics in patients with hereditary sodium channel myopathies. Our hypothesis was that propofol might interact directly with mutant channels, causing enhanced muscle excitability in affected patients. Whole-cell voltage-clamp experiments were performed on HEK 293 cells expressing R1448H mutant sodium channels. Propofol blocked sodium inward current at clinical concentrations (5 micromol/L) when depolarizing pulses were started from holding potentials close to the physiological resting potential (-70 mV). Higher propofol concentrations (>/=25 micromol/L) accelerated pathologically delayed inactivation kinetics and delayed pathologically enhanced recovery from inactivation. Our in vitro results show that inactivation-deficient sodium channels are specifically targeted and blocked by propofol. This might reduce enhanced muscle excitability experienced by affected patients in vivo.
我们在体外研究了丙泊酚对先天性副肌强直突变体骨骼肌钠通道的影响，因为在遗传性钠通道肌病患者中使用其他麻醉剂时，已观察到麻醉诱导期间严重肌肉强直导致的危及生命的并发症。我们的假设是丙泊酚可能直接与突变通道相互作用，导致受影响患者的肌肉兴奋性增强。对表达R1448H突变钠通道的HEK 293细胞进行了全细胞电压钳实验。当去极化脉冲从接近生理静息电位（-70 mV）的钳制电位开始时，丙泊酚在临床浓度（5 μmol/L）下阻断了钠内向电流。更高浓度的丙泊酚（≥25 μmol/L）加速了病理性延迟失活动力学，并延迟了病理性增强的失活后恢复。我们的体外研究结果表明，失活缺陷的钠通道是丙泊酚的特异性作用靶点并被其阻断。这可能会降低受影响患者在体内经历的增强的肌肉兴奋性。
