Browsing by Author "Figueroa, Vania"

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    Glucose increases intracellular free Ca2+ in tanycytes via ATP released through connexin 43 hemichannels
    (Wiley Periodicals, Inc., 2012) Orellana Roca, Juan Andrés; Sáez Pedraza, Pablo José; Cortés-Campos, Christian; Elizondo, Roberto J.; Shoji Sánchez, Kenji Fabricio; Contreras Duarte, Susana de las Mercedes; Figueroa, Vania; Velarde Aliaga, María Victoria; Jiang, Jean X.; Nualart, Francisco; Sáez, Juan Carlos; García, María A.
    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+ (KATP) channels, suggesting their involvement in hypothalamic glucosensing. Here, the transduction mechanism involved in the glucose-induced rise of intracellular free Ca2+ concentration ([Ca2+]i) in cultured beta-tanycytes was examined. Fura-2AM time-lapse fluorescence images revealed that glucose increases the intracellular Ca2+ 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 KATP channel-dependent pathway. Consequently, ATP export to the extracellular milieu was enhanced, resulting in activation of purinergic P2Y1 receptors followed by inositol trisphosphate receptor activation and Ca2+ release from intracellular stores. The present study identifies the mechanism by which glucose increases [Ca2+]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