Inhalational anesthetics activate two-pore-domain background K+ channels.
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.
D000595:Amino Acid Sequence; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D008195:Lymnaea; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D016062:Porosity; D015221:Potassium Channels / Q000187:drug effects*; D024683:Potassium Channels, Tandem Pore Domain; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid