Glucose inhibition persists in hypothalamic neurons lacking tandem-pore K+ channels.
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.
Guyon
Alice
A
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.
Tardy
Magalie P
MP
Rovère
Carole
C
Nahon
Jean-Louis
JL
Barhanin
Jacques
J
Lesage
Florian
F
D000818:Animals; D001464:Barium / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007031:Hypothalamus / Q000166:cytology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000172:deficiency; D024683:Potassium Channels, Tandem Pore Domain / Q000145:classification / Q000172:deficiency*; D013549:Sweetening Agents / Q000494:pharmacology*
D047908:Intracellular Signaling Peptides and Proteins; C503445:Kcnk10 protein, mouse; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000068797:Orexins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D013549:Sweetening Agents; C511784:TASK3 protein, mouse; C420132:potassium channel subfamily K member 3; D001464:Barium; D005947:Glucose