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

Nature Neuroscience volume 2, pages 422–426 (1999)Cite this article

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.

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Figure 1: Chloroform selectively activates TREK-1.
Figure 2: Halothane is a common activator of TREK-1 and TASK.
Figure 3: Isoflurane and diethyl ether differentially activate TREK-1 and TASK.
Figure 4: Clinical doses of inhalational anesthetics activate human TREK-1.
Figure 5: Volatile anesthetics stimulate TREK-1 and TASK in excised-patch configuration.
Figure 6: The C-terminal regions of TREK-1 and TASK are critical for activation by anesthetics.

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Acknowledgements

This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Association Française contre les Myopathies (AFM) and the EEC Marie Curie Program. We thank M. Jodar, N. Leroudier, G. Jarretou, V. Briet, Y. Benhamou and Dahvya Doume for technical assistance. We are grateful to C. Martin and S. Storq from Galderma (Valbonne, FRANCE) and to R. Mengual for their assistance with gas chromatography.

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  1. Institut de Pharmacologie Moléculaire et Cellulaire - CNRS - UPR 411, 660 route des Lucioles, Sophia Antipolis, Valbonne, 06560, France

    Amanda J. Patel, Eric Honoré, Florian Lesage, Michel Fink, Georges Romey & Michel Lazdunski

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  1. Amanda J. Patel
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  2. Eric Honoré
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Correspondence to Michel Lazdunski.

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Patel, A., Honoré, E., Lesage, F. et al. Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci 2, 422–426 (1999). https://doi.org/10.1038/8084

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