Haeseler G, Störmer M, Bufler J, Dengler R, Hecker H, Piepenbrock S, Leuwer M
Department of Anesthesiology, OE8050, Hannover Medical School, D-30623 Hannover, Germany.
Anesth Analg. 2001 May;92(5):1192-8. doi: 10.1097/00000539-200105000-00021.
Propofol decreases muscle tone in the absence of neuromuscular blocking drugs. This effect probably cannot be attributed solely to central nervous depression. We studied the effects of propofol on heterologously expressed skeletal muscle sodium channels. Our hypothesis was that the decrease in muscle tone may partly be attributed to an interaction of propofol with sarcolemmal sodium channels. Cells were voltage clamped and whole-cell sodium inward currents were recorded in the absence and presence of propofol. When depolarizing pulses to 0 mV were started from a holding potential close to the normal resting potential of muscle (-70 mV), or when a 2.5-s prepulse inducing slow inactivation was applied before the test pulse at -100 mV, a significant reduction in the peak current amplitude was achieved by 10 and 5 microM propofol, respectively (P < 0.001). Half-maximum blocking concentrations with these protocols were 23 and 22 microM. Blocking potency increased at depolarized membrane potentials with the fraction of inactivated channels; the estimated dissociation constant K(d) from the inactivated state was 4.6 microM. These results suggest that propofol significantly blocks sarcolemmal sodium channels at clinically relevant concentrations while maintaining potentials close to the physiological resting potential.
Voltage-gated sodium channels mediate the initiation and propagation of action potentials along the sarcolemma. Results from our study show that those channels are targeted and blocked in a concentration- and voltage-dependent manner by propofol. This mechanism may contribute to the reduction in muscle excitability.
在没有神经肌肉阻滞剂的情况下，丙泊酚可降低肌张力。这种作用可能不能仅归因于中枢神经抑制。我们研究了丙泊酚对异源表达的骨骼肌钠通道的影响。我们的假设是，肌张力降低可能部分归因于丙泊酚与肌膜钠通道的相互作用。对细胞进行电压钳制，并在有无丙泊酚的情况下记录全细胞内向钠电流。当从接近肌肉正常静息电位（-70 mV）的 holding 电位开始向 0 mV 进行去极化脉冲时，或者当在 -100 mV 的测试脉冲之前施加一个 2.5 秒的预脉冲以诱导缓慢失活时，分别用 10 和 5 μM 丙泊酚可使峰值电流幅度显著降低（P < 0.001）。采用这些方案时的半数最大阻断浓度分别为 23 和 22 μM。随着失活通道比例的增加，在去极化膜电位下阻断效力增强；从失活状态估计的解离常数 K(d) 为 4.6 μM。这些结果表明，丙泊酚在临床相关浓度下可显著阻断肌膜钠通道，同时保持电位接近生理静息电位。
电压门控钠通道介导动作电位沿肌膜的起始和传播。我们的研究结果表明，这些通道被丙泊酚以浓度和电压依赖性方式靶向阻断。这种机制可能有助于降低肌肉兴奋性。
