Abstract
Glucose sensing by hypothalamic neurons triggers adaptive metabolic and behavioral responses. In orexin neurons, extracellular glucose activates a leak K(+) current promoting electrical activity inhibition. Sensitivity to external acidification and halothane, and resistance to ruthenium red designated the tandem-pore K(+) (K(2P)) channel subunit TASK3 as part of the glucose-induced channel. Here, we show that glucose inhibition and its pH sensitivity persist in mice lacking TASK3 or TASK1, or both subunits. We also tested the implication of another class of K(2P) channels activated by halothane. In the corresponding TREK1/2/TRAAK triple knock-out mice, glucose inhibition persisted in hypothalamic neurons ruling out a major contribution of these subunits to the glucose-activated K(+) conductance. Finally, block of this glucose-induced hyperpolarizing current by low Ba(2+) concentrations was consistent with the conclusion that K(2P) channels are not required for glucosensing in hypothalamic neurons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Barium / pharmacology
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Glucose / pharmacology*
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Hydrogen-Ion Concentration
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Hypothalamus / cytology*
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins / metabolism
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Male
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nerve Tissue Proteins / deficiency
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Neural Inhibition / drug effects*
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Neural Inhibition / physiology
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Neurons / drug effects*
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Neurons / physiology
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Neuropeptides / metabolism
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Orexins
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Patch-Clamp Techniques / methods
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Potassium Channels / deficiency
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Potassium Channels, Tandem Pore Domain / classification
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Potassium Channels, Tandem Pore Domain / deficiency*
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Sweetening Agents / pharmacology*
Substances
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Intracellular Signaling Peptides and Proteins
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Kcnk10 protein, mouse
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Nerve Tissue Proteins
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Neuropeptides
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Orexins
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Potassium Channels
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Potassium Channels, Tandem Pore Domain
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Sweetening Agents
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TASK3 protein, mouse
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potassium channel subfamily K member 3
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Barium
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Glucose