Effects of volatile anaesthetics 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 neuronal ion channels, but may also involve alterations in the ion composition of the extracellular space. Since glial cells play a key role in regulating the extracellular ion composition in the brains of mammals, we analyzed the effects of halothane, isoflurane and enflurane on the membrane conductances and ion channels of cultured cortical astrocytes. Astrocytes were dissociated from the neocortex of 0-2-day old rats and grown in culture for 3-4 weeks. Anaesthetic-induced changes in the membrane potential were recorded in the whole cell current-clamp configuration of the patch-clamp technique. We further studied the effects of halothane and enflurane on single ion channels in excised membrane patches. At concentrations corresponding to 1-2 MAC (1 MAC induces general anaesthesia in 50% of the patients and rats), membrane potentials recorded in the presence of enflurane, isoflurane and halothane did not differ significantly from the control values. At higher concentrations, effects of enflurane and halothane, but not of isoflurane, were statistically significant. Single-channel recordings revealed that halothane and enflurane activated a high conductance anion channel, which possibly mediated the effects observed during whole cell recordings. In less than 10% of the membrane patches, volatile anaesthetics either increased or decreased the mean open time of K+-selective ion channels without altering single-channel conductances. In summary, it seems unlikely that the actions of volatile anaesthetics described here are involved in the state of general anaesthesia. Statistically significant effects occurred at concentrations ten times higher than those required to cause half-maximal depression of action potential firing of neocortical neurons in cultured brain slices. However, it cannot be excluded that the changes observed in the membrane conductance of cortical astrocytes disturb the physiological function of these cells, thereby influencing the membrane resting potential of neurons.
Felisberti
F
F
Psychology Department, University Park Nottingham, UK.
Antkowiak
B
B
Kirschfeld
K
K
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000378:metabolism; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects*; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D019579:Neocortex / Q000166:cytology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D000838:Anions; D018118:Chloride Channels; D015221:Potassium Channels; D004737:Enflurane; D007530:Isoflurane; D011188:Potassium; D006221:Halothane