Molecular aspects of inhalational anaesthetic interaction with excitable and non-excitable membranes.

The interaction of three volatile general anaesthetics (halothane, enflurane and methoxyflurane) with erythrocyte membranes at concentrations causing protection of intact erythrocytes against hypotonic lysis was investigated in the hope of deriving fundamental information regarding the membrane perturbational characteristics of these substances as compared with those of local anaesthetics studied previously. The volatile agents increased the susceptibility of membrane proteins and, to a somewhat lesser extent, of phospholipids to trinitrophenylation of picryl chloride or trinitrobenzenesulfonic acid but decreased the accessibility of membrane protein sulfhydryl groups to modification by 5,5'-dithio-bis-(2-nitrobenzoic acid). These observations stood in marked contrast to our previous findings with local anaesthetics, in that these substances, when compared to general anaesthetics at concentrations producing equivalent erythrocyte stabilization, caused a greater enhancement of trinitrophenylation, largely restricted to the phospholipid component and an increased exposure of membrane sulfhydryl groups. Further evidence for alterations in membrane proteins produced by concentrations of volatile anaesthetics relevant to surgical anaesthesia was obtained from the observation that all three agents produced significant decreases in the activation energy of membrane-bound p-nitrophenylphosphatases. Preliminary experiments with brain synaptic membranes suggested that the structural and functional consequences of membrane-anaesthetic interaction in erythrocytes are relevant to the situation in excitable tissues. Our results indicate, therefore, that general and local anaesthetics cause distinctly different alterations in the properties of model membrane systems and this may reflect corresponding differences in the molecular mechanisms by which these groups of agents produce their anaesthetic actions.