Abstract
Inhibition of "leak" potassium (K+) channels is a widespread CNS mechanism by which transmitters induce slow excitation. We show that TASK-1, a two pore domain K+ channel, provides a prominent leak K+ current and target for neurotransmitter modulation in hypoglossal motoneurons (HMs). TASK-1 mRNA is present at high levels in motoneurons, including HMs, which express a K+ current with pH- and voltage-dependent properties virtually identical to those of the cloned channel. This pH-sensitive K+ channel was fully inhibited by serotonin, norepinephrine, substance P, thyrotropin-releasing hormone, and 3,5-dihydroxyphenylglycine, a group I metabotropic glutamate receptor agonist. The neurotransmitter effect was entirely reconstituted in HEK 293 cells coexpressing TASK-1 and the TRH-R1 receptor. Given its expression patterns and the widespread prevalence of this neuromodulatory mechanism, TASK-1 also likely supports this action in other CNS neurons.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acids / pharmacology
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Animals
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Animals, Newborn
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Cell Line
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Electric Conductivity
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Gene Expression / physiology
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Glutamic Acid / metabolism
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Humans
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Hydrogen-Ion Concentration
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Hypoglossal Nerve / cytology
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Kidney / cytology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Motor Neurons / chemistry
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Motor Neurons / metabolism*
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Nerve Tissue Proteins
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Neurotransmitter Agents / metabolism*
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Norepinephrine / metabolism
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Patch-Clamp Techniques
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Potassium / metabolism
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Potassium Channels / chemistry
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Potassium Channels, Tandem Pore Domain*
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Protein Structure, Tertiary
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RNA, Messenger / analysis
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Rats
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Rats, Sprague-Dawley
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Serotonin / metabolism
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Substance P / metabolism
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Thyrotropin-Releasing Hormone / metabolism
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Transfection
Substances
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Acids
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Nerve Tissue Proteins
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Neurotransmitter Agents
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Potassium Channels
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Potassium Channels, Tandem Pore Domain
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RNA, Messenger
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potassium channel subfamily K member 3
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Serotonin
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Substance P
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Glutamic Acid
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Thyrotropin-Releasing Hormone
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Potassium
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Norepinephrine