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Glucose increases intracellular free Ca 2+ in tanycytes via ATP released through connexin 43 hemichannels
Author(s) -
Orellana Juan A.,
Sáez Pablo J.,
Cortéscampos Christian,
Elizondo Roberto J.,
Shoji Kenji F.,
ContrerasDuarte Susana,
Figueroa Vania,
Velarde Victoria,
Jiang Jean X.,
Nualart Francisco,
Sáez Juan C.,
García María A.
Publication year - 2012
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21246
Subject(s) - extracellular , biology , intracellular , microbiology and biotechnology , connexin , carbenoxolone , purinergic receptor , pannexin , signal transduction , gap junction , biochemistry
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. © 2011 Wiley Periodicals, Inc.