The Journal of Neuroscience, February 25, 2009, 29(8):2528-2533; doi:10.1523/JNEUROSCI.5764-08.2009
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Brief Communications
Glucose Inhibition Persists in Hypothalamic Neurons Lacking Tandem-Pore K+ Channels
Alice Guyon,
Magalie P. Tardy,
Carole Rovère,
Jean-Louis Nahon, *
Jacques Barhanin, * and
Florian Lesage *
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6097, Université de Nice Sophia-Antipolis, 06560 Valbonne, France
Correspondence should be addressed to Florian Lesage, Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, 660 Route des Lucioles, 06560 Valbonne Sophia-Antipolis, France. Email: lesage{at}ipmc.cnrs.fr
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+ (K2P) 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 K2P 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 Ba2+ concentrations was consistent with the conclusion that K2P channels are not required for glucosensing in hypothalamic neurons.
Key words: orexin neuron; leak potassium channel; resting potential; gene inactivation; neuropeptide; secretion
Received Dec. 3, 2008;
revised Jan. 20, 2009;
accepted Jan. 22, 2009.
Correspondence should be addressed to Florian Lesage, Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, 660 Route des Lucioles, 06560 Valbonne Sophia-Antipolis, France. Email: lesage{at}ipmc.cnrs.fr