Mechanisms of propofol action on ion currents in the myelinated axon of Xenopus laevis.
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 microM 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 (INa,IK), (ii) a voltage-independent block of INa, but not of IK, and (iii) a slowed time course of IK 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 INa block showed 1:1 stoichiometry and 50% reduction at 2.7 mM. The slowed IK 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.
Veintemilla
F
F
Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm, Sweden.
Elinder
F
F
Arhem
P
P
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects; D013997:Time Factors; D014982:Xenopus laevis
D000777:Anesthetics; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D015742:Propofol