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J Neurosci

Title:		Shaker-related potassium channels in the central medial nucleus of the thalamus are important molecular targets for arousal suppression by volatile general anesthetics
Author(s):		Lioudyno MI; Birch AM; Tanaka BS; Sokolov Y; Goldin AL; Chandy KG; Hall JE; Alkire MT;
Address:		"Department of Physiology and Biophysics, University of California, Irvine, Irvine, California 92697-4561, Center for the Neurobiology of Learning and Memory and Department of Anesthesiology and Perioperative Care, University of California, Irvine, Orange, California 92868, and Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California 92697-4025"
Journal Title:		J Neurosci
Year:		2013
Volume:		33
Issue:		41
Page Number:		16310 - 16322
DOI:		10.1523/JNEUROSCI.0344-13.2013
ISSN/ISBN:		1529-2401 (Electronic) 0270-6474 (Print) 0270-6474 (Linking)
Abstract:		"The molecular targets and neural circuits that underlie general anesthesia are not fully elucidated. Here, we directly demonstrate that Kv1-family (Shaker-related) delayed rectifier K(+) channels in the central medial thalamic nucleus (CMT) are important targets for volatile anesthetics. The modulation of Kv1 channels by volatiles is network specific as microinfusion of ShK, a potent inhibitor of Kv1.1, Kv1.3, and Kv1.6 channels, into the CMT awakened sevoflurane-anesthetized rodents. In heterologous expression systems, sevoflurane, isoflurane, and desflurane at subsurgical concentrations potentiated delayed rectifier Kv1 channels at low depolarizing potentials. In mouse thalamic brain slices, sevoflurane inhibited firing frequency and delayed the onset of action potentials in CMT neurons, and ShK-186, a Kv1.3-selective inhibitor, prevented these effects. Our findings demonstrate the exquisite sensitivity of delayed rectifier Kv1 channels to modulation by volatile anesthetics and highlight an arousal suppressing role of Kv1 channels in CMT neurons during the process of anesthesia"
Keywords:		"Action Potentials/drug effects Anesthetics, General/*pharmacology Animals Arousal/*drug effects Desflurane Intralaminar Thalamic Nuclei/*drug effects/metabolism Isoflurane/analogs & derivatives/pharmacology Magnetic Resonance Spectroscopy Male Methyl Ethe;"
Notes:		"MedlineLioudyno, Maria I Birch, Alexandra M Tanaka, Brian S Sokolov, Yuri Goldin, Alan L Chandy, K George Hall, James E Alkire, Michael T eng 1P01 AG032131/AG/NIA NIH HHS/ R01 NS048252/NS/NINDS NIH HHS/ NS048336/NS/NINDS NIH HHS/ P01 AG032131/AG/NIA NIH HHS/ R01 NS048336/NS/NINDS NIH HHS/ R01 NS48252/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural 2013/10/11 J Neurosci. 2013 Oct 9; 33(41):16310-22. doi: 10.1523/JNEUROSCI.0344-13.2013"