title: Glucose increases intracellular free Ca(2+)  in tanycytes via ATP released through connexin 43 hemichannels.
abstract: The ventromedial hypothalamus is involved in regulating feeding and satiety behavior, and its neurons interact with specialized ependymal-glial cells, termed tanycytes. The latter express glucose-sensing proteins, including glucose transporter 2, glucokinase, and ATP-sensitive K(+) (K(ATP) ) channels, suggesting their involvement in hypothalamic glucosensing. Here, the transduction mechanism involved in the glucose-induced rise of intracellular free Ca(2+) concentration ([Ca(2+) ](i) ) in cultured β-tanycytes was examined. Fura-2AM time-lapse fluorescence images revealed that glucose increases the intracellular Ca(2+) signal in a concentration-dependent manner. Glucose transportation, primarily via glucose transporters, and metabolism via anaerobic glycolysis increased connexin 43 (Cx43) hemichannel activity, evaluated by ethidium uptake and whole cell patch clamp recordings, through a K(ATP) channel-dependent pathway. Consequently, ATP export to the extracellular milieu was enhanced, resulting in activation of purinergic P2Y(1) receptors followed by inositol trisphosphate receptor activation and Ca(2+) release from intracellular stores. The present study identifies the mechanism by which glucose increases [Ca(2+) ](i) in tanycytes. It also establishes that Cx43 hemichannels can be rapidly activated under physiological conditions by the sequential activation of glucosensing proteins in normal tanycytes.
authors: Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago, Chile. jaorella@uc.cl
authors: Juan A
authors: JA
authors: Orellana
authors: Pablo J
authors: PJ
authors: Sáez
authors: Christian
authors: C
authors: Cortés-Campos
authors: Roberto J
authors: RJ
authors: Elizondo
authors: Kenji F
authors: KF
authors: Shoji
authors: Susana
authors: S
authors: Contreras-Duarte
authors: Vania
authors: V
authors: Figueroa
authors: Victoria
authors: V
authors: Velarde
authors: Jean X
authors: JX
authors: Jiang
authors: Francisco
authors: F
authors: Nualart
authors: Juan C
authors: JC
authors: Sáez
authors: María A
authors: MA
authors: García
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002412:Cations / Q000378:metabolism; D002478:Cells, Cultured; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology; D007424:Intracellular Fluid / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D002412:Cations; D018031:Connexin 43; D004791:Enzyme Inhibitors; D050491:Glutamate Plasma Membrane Transport Proteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D014841:von Willebrand Factor; D003571:Cytochalasin B; D000255:Adenosine Triphosphate; D005941:Glucokinase; D005947:Glucose; D011339:Probenecid; D002118:Calcium