Effects of intravenous anaesthetics on nerve axons.
The effects of ketamine, etomidate, alphaxalone and alphadolone acetate on nodal sodium and potassium currents of frog myelinated nerve fibre have been examined. The four general anaesthetics reversibly depressed ionic currents, although they tended to be more effective in blocking potassium than sodium current. The potassium current was reduced by etomidate and alphaxalone in a time-dependent manner. This was not found for ketamine and alphadolone acetate. In addition to blocking effects on sodium current, etomidate, alphaxalone and alphadolone acetate, but not ketamine, induced a negative shift of steady-state sodium inactivation-voltage curves. Collectively, the general anaesthetics appeared to alter specifically and differentially sodium and potassium channel-gating systems. The simplest interpretation of these results suggests that the compounds produce state-dependent blocks of ionic channels, and that there are general anaesthetic receptor sites located on the channel proteins themselves. Furthermore, potassium and sodium channels may contain several types of receptor sites, through which anaesthetics could exert their different actions.
Benoit
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Laboratoire de Physiologie Cellulaire, URA CNRS 1121, Université de Paris Sud, Orsay, France.
D000200:Action Potentials / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000008:administration & dosage / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011277:Pregnanediones / Q000008:administration & dosage / Q000494:pharmacology; D011893:Rana esculenta; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects*; D013997:Time Factors
D018686:Anesthetics, Intravenous; D015221:Potassium Channels; D011277:Pregnanediones; D015222:Sodium Channels; D007649:Ketamine; D012964:Sodium; C006477:alphaxalone; C033418:alphadolone; D011188:Potassium; D005045:Etomidate