[The molecular action profile of intravenous anesthetics]

A close look at the molecular interactions of intravenous anaesthetics reveals a complex and non-uniform picture. A multitude of membrane structures are affected by the individual anaesthetic compounds, although with specific differential profiles of molecular action for the different groups of anaesthetic substances. This is consistent with the hypothesis of a multi-mechanistic mode of action, where anaesthesia results from the superposition and integration of several anaesthetic actions on the molecular level. This overall concept is illustrated by using the well characterised voltage-activated human brain sodium channel protein and its interactions with various intravenous anaesthetics as an example for other membrane proteins. Using the novel lipid bilayer "voltage-clamp" technique, single sodium channels were incorporated into artificial lipid bilayers and their single channel properties studied. Compared to controls, all studied anaesthetics (propofol, pentobarbital, ketamine, midazolam) interacted in a dose-dependent manner with two key sodium channel functions: 1. reduction of the voltage-independent fractional channel open-time and 2. interaction with the voltage-dependent steady-state activation process. Only propofol and pentobarbital demonstrated these effects at clinically relevant concentrations; hence, the sodium channel might serve as a molecular site of action for these substances only. Differences between clinical anaesthetics and their clinical actions may thus correlate with differential molecular sites and modes of action.