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

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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.