Inhalational Anesthetics Activate Two-Pore-Domain Background K+ Channels

Nat Neurosci. 1999 May;2(5):422-6. doi: 10.1038/8084.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • COS Cells
  • Lymnaea
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Neurons / drug effects*
  • Patch-Clamp Techniques
  • Porosity
  • Potassium Channels / drug effects*
  • Potassium Channels, Tandem Pore Domain*
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid

Substances

  • Anesthetics, Inhalation
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1
  • potassium channel subfamily K member 3