Volatile General Anaesthetics Activate a Novel Neuronal K+ Current

Although it is still controversial whether the primary target sites underlying general anaesthesia are proteins or lipids, it is generally thought that the ultimate targets are ion channels in nerve membranes. One approach to finding these targets is to study the effects of general anaesthetics on identified neurons, where differential effects on neuronal activity can be pursued to the molecular level. Here we report that amongst a group of apparently identical molluscan neurons having endogenous firing activity, a single cell displays an unusual sensitivity to volatile agents (which, at surgical levels, completely inhibit its activity). We further show that this sensitivity is due to a novel anaesthetic-activated K+ current, which is found in the sensitive cell but not in the surrounding insensitive cells. This K+ conductance is not appreciably voltage-gated and persists for as long as the anaesthetic is present. The response to anaesthetics is completely reversible and saturates at low anaesthetic partial pressures: the half-maximal response for halothane occurs at 0.0063 atm, close to its minimum alveolar concentration (0.0075 atm) in man.