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Inhalational anesthetics activate two-pore-domain background K+ channels

A J Patel1, E Honoré, F Lesage

  • 1Institut de Pharmacologie Moléculaire et Cellulaire-CNRS-UPR 411, Valbonne, France.

Nature Neuroscience
|May 13, 1999
PubMed

Volatile anesthetics produce safe, reversible unconsciousness, amnesia and analgesia via hyperpolarization of mammalian neurons. In molluscan pacemaker neurons, they activate an inhibitory synaptic K+ current (IKAn), proposed to be important in general anesthesia. Here we show that TASK and TREK-1, two recently cloned mammalian two-P-domain K+ channels similar to IKAn in biophysical properties, are activated by volatile general anesthetics. Chloroform, diethyl ether, halothane and isoflurane activated TREK-1, whereas only halothane and isoflurane activated TASK. Carboxy (C)-terminal regions were critical for anesthetic activation in both channels. Thus both TREK-1 and TASK are possibly important target sites for these agents.

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