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The Journal of Neuroscience, September 1, 2000, 20(17):6347-6354
The TASK-1 Two-Pore Domain K+ Channel Is a
Molecular Substrate for Neuronal Effects of Inhalation Anesthetics
Jay E.
Sirois1,
Qiubo
Lei1,
Edmund M.
Talley1,
Carl
Lynch III2, and
Douglas A.
Bayliss1
Departments of 1 Pharmacology and
2 Anesthesiology, School of Medicine, University of
Virginia, Charlottesville, Virginia 22908
Despite widespread use of volatile general anesthetics for well
over a century, the mechanisms by which they alter specific CNS
functions remain unclear. Here, we present evidence 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, two populations
of neurons that express TASK-1 mRNA, inhalation anesthetics activated a
neuronal K+ conductance, causing membrane
hyperpolarization and suppressing action potential discharge. These
membrane effects occurred at clinically relevant anesthetic levels,
with precisely the steep concentration dependence expected for
anesthetic effects of these compounds. The native neuronal
K+ current displayed voltage- and time-dependent
properties that were identical to those mediated by the open-rectifier
TASK-1 channel. Moreover, the neuronal K+ channel
and heterologously expressed TASK-1 were similarly modulated by
extracellular pH. The decreased cellular excitability associated with
TASK-1 activation in these cell groups probably accounts for specific
CNS effects of anesthetics: in motoneurons, it likely contributes to
anesthetic-induced immobilization, whereas in the locus coeruleus, it
may support analgesic and hypnotic actions attributed to inhibition of
those neurons.
Key words:
two-pore domain K+ channel; TASK-1; pH-sensitive; volatile anesthetic; motor neuron; locus
coeruleus neuron
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176347-08$05.00/0
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|
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|
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|
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|
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|
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|

|
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[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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[Abstract]
[Full Text]
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|
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|

|
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|
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[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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909 - 910.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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91(1):
40 - 49.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function
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100(13):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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3(4):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
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50(90001):
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[Full Text]
|
 |
|

|
 |

|
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96(5):
1340 - 1344.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
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May 1, 2003;
96(5):
1345 - 1349.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K+ channel
Cardiovasc Res,
April 1, 2003;
58(1):
46 - 54.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Czirjak and P. Enyedi
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Mol. Pharmacol.,
March 1, 2003;
63(3):
646 - 652.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Two-Pore-Domain (Kcnk) Potassium Channels: Dynamic Roles in Neuronal Function
Neuroscientist,
February 1, 2003;
9(1):
46 - 56.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Perez-Reyes
Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels
Physiol Rev,
January 1, 2003;
83(1):
117 - 161.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K+ and Ca2+ channels
Am J Physiol Cell Physiol,
January 1, 2003;
284(1):
C145 - C155.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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J. Biol. Chem.,
May 10, 2002;
277(20):
17733 - 17742.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Serotonergic Raphe Neurons Express TASK Channel Transcripts and a TASK-Like pH- and Halothane-Sensitive K+ Conductance
J. Neurosci.,
February 15, 2002;
22(4):
1256 - 1265.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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CNS Distribution of Members of the Two-Pore-Domain (KCNK) Potassium Channel Family
J. Neurosci.,
October 1, 2001;
21(19):
7491 - 7505.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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General Anesthetic Potencies of a Series of Propofol Analogs Correlate with Potency for Potentiation of {gamma}-Aminobutyric Acid (GABA) Current at the GABAA Receptor but Not with Lipid Solubility
J. Pharmacol. Exp. Ther.,
April 1, 2001;
297(1):
338 - 351.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
A. Walcourt, R. L. Scott, and H. A. Nash
Blockage of One Class of Potassium Channel Alters the Effectiveness of Halothane in a Brain Circuit of Drosophila
Anesth. Analg.,
February 1, 2001;
92(2):
535 - 541.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Block of Kcnk3 by Protons. EVIDENCE THAT 2-P-DOMAIN POTASSIUM CHANNEL SUBUNITS FUNCTION AS HOMODIMERS
J. Biol. Chem.,
June 29, 2001;
276(27):
24449 - 24452.
[Abstract]
[Full Text]
[PDF]
|
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|

|
 |

|
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Combined Antisense and Pharmacological Approaches Implicate hTASK as an Airway O2 Sensing K+ Channel
J. Biol. Chem.,
July 6, 2001;
276(28):
26499 - 26508.
[Abstract]
[Full Text]
[PDF]
|
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|
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|
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W. Gu, G. Schlichthorl, J. R. Hirsch, H. Engels, C. Karschin, A. Karschin, C. Derst, O. K. Steinlein, and J. Daut
Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2
J. Physiol.,
March 15, 2002;
539(3):
657 - 668.
[Abstract]
[Full Text]
[PDF]
|
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|
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