Effect of sevoflurane on the voltage-dependent sodium currents in a Lymnaea neuron

背景：电压依赖性钠电流（INa^+）与神经元兴奋性和麻醉有关。为探讨七氟醚影响INa^+的麻醉机制，采用细胞膜片钳技术和电流钳技术，比较了七氟醚和利多卡因对神经细胞膜电位和INa^+的影响。细胞外或细胞内灌注七氟烷。在七氟醚的外部和内部灌注中测量INa+的动作电位幅度、电流-电压曲线和稳态失活曲线。七氟烷外部灌注抑制了动作电位的幅度[对照组为61.8 ± 7.6（mV），0.4 mM时为43.8 ± 7.1，2 mM时为4.8 ± 3.6，和0.9 ± 0.8（4 mM）]和INa^+ [80 ± 11%（0.4 mM）、59 ± 12%（2 mM）和48 ± 12%（4 mM）]，呈浓度依赖性。然而，在内部灌注的情况下，七氟烷不会抑制这些参数。相反，内灌注利多卡因抑制INa+。无论是外部还是内部灌注的七氟醚利多卡因的稳态失活曲线没有移动。结论：七氟醚作为细胞外塞抑制电压依赖性钠电流。

Background : The voltage-dependent sodium currents (INa^+) are related to neuron excitability and anesthesia. To clarify the anesthetic mechanism of sevoflurane affecting INa^+, the effects of sevoflurane and lidocaine on INa^+ were compared using a neuron from Lymnaea stagnalis.Methods : The effects of sevoflurane and lidocaine on the membrane potential and INa+ were measured using current clamp and whole cell patch-clamp configuration. Sevoflurane was perfused either extra-cellularly or intra-cellularly. The amplitude of action potential, current voltage curves, and steady-state inactivation curves for INa+ were measured following in external and internal perfusion of sevoflurane.Results : External perfusion with sevoflurane suppressed the amplitude of the action potential [61.8 ± 7.6 (mV) in the controls, 43.8 ± 7.1 at 0.4 mM, 4.8 ± 3.6 at 2 mM, and 0.9 ± 0.8 at 4 mM], and INa^+ [80 ± 11% at 0.4 mM, 59 ± 12 % at 2 mM, and 48 ± 12 % at 4 mM] in a concentration-dependent manner. However, with internal perfusion, sevoflurane did not suppress these parameters. Conversely, internal perfusion of lidocaine suppressed INa+. The steady-state inactivation curves were not shifted by either external or internal perfusion of sevoflurane as lidocaine.Conclusion : Sevoflurane acts as an extra-cellular plug to suppress the voltage-dependent sodium currents.