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

@article{Patel1999InhalationalAA,
  title={Inhalational anesthetics activate two-pore-domain background K+ channels},
  author={Amanda Patel and Eric Honor{\'e} and Florian Lesage and Michel Fink and Georges Romey and Michel Lazdunski},
  journal={Nature Neuroscience},
  year={1999},
  volume={2},
  pages={422-426}
}
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… 
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625 Citations
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625 Citations

Anesthetic-sensitive 2P Domain K+ Channels
TLDR
The expression and properties of these anesthetic-sensitive K channels are reviewed, and their possible functional role in the mechanisms of anesthesia and analgesia is discussed.
2P domain K+ channels: novel targets for volatile general anaesthetics
The volatile anaesthetic-mediated hyperpolarization reduces cell excitability, increases synaptic input conductance, and may contribute to the depression of the central nervous system. Background K+…
The Effect of Halothane and Isoflurane on KCNK2 Transfected HEK-293 Cells
TLDR
Patel et al reported that inhalational volatile anesthetics including chloroform, ether, halothane, and isoflurane modulate KCNK activity in transfected COS-7 and HEK-293 cells and suggested that KCNK2 and KCNK3 are critical mediators of the central actions of volatile generalAnesthetics, based on their hyperpolarizing actions.
The TASK-1 Two-Pore Domain K+ Channel Is a Molecular Substrate for Neuronal Effects of Inhalation Anesthetics
TLDR
Evidence is presented implicating the two-pore domain, pH-sensitive TASK-1 channel as a target for specific, clinically important anesthetic effects in mammalian neurons, in rat somatic motoneurons and locus coeruleus cells.
Potent Activation of the Human Tandem Pore Domain K Channel TRESK with Clinical Concentrations of Volatile Anesthetics
TLDR
The results identify TRESK as a target of volatile anesthetics and suggest a role for this background K channel in mediating the effects of inhaled anesthetic effects in the central nervous system.
HCN Subunit-Specific and cAMP-Modulated Effects of Anesthetics on Neuronal Pacemaker Currents
TLDR
Data reveal a molecular basis for multiple actions of anesthetics on neuronal HCN channels, highlight the importance of proximal C terminus in modulation of HCN channel gating by diverse agents, and advance neuronal pacemaker channels as potentially relevant targets for clinical actions of inhaled anesthetic.
HCN and K2P Channels in Anesthetic Mechanisms Research.
Motoneuronal TASK Channels Contribute to Immobilizing Effects of Inhalational General Anesthetics
TLDR
Data indicate that TASK channels in cholinergic neurons are molecular substrates for select actions of inhaled anesthetics; for immobilization, which is spinally mediated, these data implicate motoneurons as the likely neuronal substrates.
Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1.
TLDR
It is concluded that intravenous and volatile anesthetics have dissimilar effects on K(2P) channels.
Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane.
TLDR
It is shown that certain members of the two-pore-domain K+ channel superfamily may represent an important new target for these gaseous anesthetics and that Glu306, an amino acid that has previously been found to be important in the modulation of TREK-1 by arachidonic acid, membrane stretch and internal pH, is critical for the activating effects of the anesthetic gases.
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References

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