Journal
GLIA
Volume 60, Issue 1, Pages 53-68Publisher
WILEY-BLACKWELL
DOI: 10.1002/glia.21246
Keywords
glucosensing; hypothalamus; glucokinase; connexons
Categories
Funding
- CONICYT [24080055]
- FONDECYT [1100705, 1111033, 1100396]
- FONDEF [DO7I1086]
- Anillo [ACT-71]
- NIH [ARO46798]
- Welch Foundation [AQ-1507]
- NATIONAL EYE INSTITUTE [R01EY012085] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [P01AR046798] Funding Source: NIH RePORTER
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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. (C) 2011 Wiley Periodicals, Inc.
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