Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics

Roman M. Lazarenko, Sarah C. Willcox, Shaofang Shu, Allison P. Berg, Vesna Jevtovic-Todorovic, Edmund M. Talley, Xiangdong Chen, Douglas A. Bayliss

Research output: Contribution to journalArticle

Abstract

General anesthetics cause sedation, hypnosis, and immobilization via CNS mechanisms that remain incompletely understood; contributions of particular anesthetic targets in specific neural pathways remain largely unexplored. Among potential molecular targets for mediating anesthetic actions, members of the TASK subgroup [TASK-1 (K2P3.1) and TASK-3 (K2P9.1)] of background K+ channels are appealing candidates since they are expressed in CNS sites relevant to anesthetic actions and activated by clinically relevant concentrations of inhaled anesthetics. Here, we used global and conditional TASK channel single and double subunit knock-out mice to demonstrate definitively that TASK channels account for motoneuronal, anesthetic-activated K+ currents and to test their contributions to sedative, hypnotic, and immobilizing anesthetic actions. In motoneurons from all knock-out mice lines, TASK-like currents were reduced and cells were less sensitive to hyperpolarizing effects of halothane and isoflurane. In an immobilization assay, higher concentrations of both halothane and isoflurane were required to render TASK knock-out animals unresponsive to a tail pinch; in assays of sedation (loss of movement) and hypnosis (loss-of-righting reflex), TASK knock-out mice showed a modest decrease in sensitivity, and only for halothane. In conditional knock-out mice, with TASK channel deletion restricted to cholinergic neurons, immobilizing actions of the inhaled anesthetics and sedative effects of halothane were reduced to the same extent as in global knock-out lines. These 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. Copyright

Original languageEnglish (US)
Pages (from-to)7691-7704
Number of pages14
JournalJournal of Neuroscience
Volume30
Issue number22
DOIs
StatePublished - Jun 2 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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    Lazarenko, R. M., Willcox, S. C., Shu, S., Berg, A. P., Jevtovic-Todorovic, V., Talley, E. M., Chen, X., & Bayliss, D. A. (2010). Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics. Journal of Neuroscience, 30(22), 7691-7704. https://doi.org/10.1523/JNEUROSCI.1655-10.2010