EFFECTS OF VOLATILE ANESTHETICS ON THE MEMBRANE-POTENTIAL AND ION CHANNELS OF CULTURED NEOCORTICAL ASTROCYTES

Volatile anaesthetics cause changes in the membrane resting potential of central neurons. This effect probably arises from actions on neuron al ion channels, but may also involve alterations in the ion compositi on of the extracellular space. Since glial cells play a key role in re gulating the extracellular ion composition in the brains of mammals, w e analyzed the effects of halothane, isoflurane and enflurane on the m embrane conductances and ion channels of cultured cortical astrocytes. Astrocytes were dissociated from the neocortex of 0-2-day old rats an d grown in culture for 3-4 weeks. Anaesthetic-induced changes in the m embrane potential were recorded in the whole cell current-clamp config uration of the patch-clamp technique. We further studied the effects o f halothane and enflurane on single ion channels in excised membrane p atches. At concentrations corresponding to 1-2 MAC (1 MAC induces gene ral anaesthesia in 50% of the patients and rats), membrane potentials recorded in the presence of enflurane, isoflurane and halothane did no t differ significantly from the control values. At higher concentratio ns, effects of enflurane and halothane, but not of isoflurane, were st atistically significant. Single-channel recordings revealed that halot hane and enflurane activated a high conductance anion channel, which p ossibly mediated the effects observed during whole cell recordings. In less than 10% of the membrane patches, volatile anaesthetics either i ncreased or decreased the mean open time of K+-selective ion channels without altering single-channel conductances. In summary, it seems unl ikely that the actions of volatile anaesthetics described here are inv olved in the state of general anaesthesia. Statistically significant e ffects occurred at concentrations ten times higher than those required to cause half-maximal depression of action potential firing of neocor tical neurons in cultured brain slices. However, it cannot be excluded that the changes observed in the membrane conductance of cortical ast rocytes disturb the physiological function of these cells, thereby inf luencing the membrane resting potential of neurons. (C) 1997 Elsevier Science B.V.