Mechanisms of propofol action on ion currents in the myelinated axon of Xenopus laevis

Abstract

The effect of the intravenous anaesthetic, propofol (2,6-diisopropylphenol), was investigated on frog myelinated axons under voltage-clamp conditions. The effect, in the concentration range 60 μM to 10 mM, was a combination of (i) a negative shift of the steady state activation and inactivation curves for both Na + and K + currents (I Na),I K, (ii) a voltage-independent block of I Na, but not of I K, and (iii) a slowed time course of I K activation. The shift was dose-dependent and, at 1 mM, about −10 mV for the activation and −16 mV for the inactivation curves. The voltage-independent I Na block showed 1:1 stoichiometry and 50% reduction at 2.7 mM. The slowed I K activation showed saturation at 1 mM with a doubled time to half steady state value. All the effects were only partially reversible and showed a complex time course at application and washing. The shift of potential dependence may be explained by a general effect on the membrane electric field. The findings suggest effects directly on channel proteins as well as on membrane lipids.