A New ATP-Sensitive K+ Channel–Independent Mechanism Is Involved in Glucose-Excited Neurons of Mouse Arcuate Nucleus

• Published in: Diabetes (New York, N.Y.) Vol. 53; no. 11; pp. 2767 - 2775
• Main Authors: FIORAMONTI, Xavier, LORSIGNOL, Anne, TAUPIGNON, Anne, PENICAUD, Luc
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.11.2004
• Subjects: Animals; Arcuate Nucleus of Hypothalamus - physiology; Biological and medical sciences; Cesium - pharmacology; Chlorides - pharmacology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Food and Nutrition; Glucose - pharmacology; Glucose - physiology; In Vitro Techniques; Life Sciences; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Mice, Knockout; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying - deficiency; Potassium Channels, Inwardly Rectifying - genetics; Potassium Channels, Inwardly Rectifying - physiology; Tetrodotoxin - pharmacology; Endocrinopathy; Diabetes mellitus; Arcuate nucleus; Rodentia; Central nervous system; Ionic channel; Hypothalamus; Glucose; Inorganic element; Encephalon; Vertebrata; Mammalia; Neuron; Mouse; Animal; ATP; Potassium; high glucose excited; high glucose inhibited; HGE; ventromedial hypothalamus; HGI; VMH; ventromedian nucleus; ARC; arcuate nucleus; VMN; TTX; tetrodotoxin; KATP channel; ATP-sensitive K+ channel
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.53.11.2767

A New ATP-Sensitive K + Channel–Independent Mechanism Is Involved in Glucose-Excited Neurons of Mouse Arcuate Nucleus Xavier Fioramonti 1 , Anne Lorsignol 1 , Anne Taupignon 2 and Luc Pénicaud 1 1 CNRS UMR 5018, Paul Sabatier University, Toulouse, France 2 CNRS UMR 5543, Victor Segalen University, Bordeaux, France Address correspondence and reprint requests to Dr. Anne Lorsignol, UMR 5018 CNRS-UPS, IFR 31, CHU Rangueil, 1 Avenue Jean Poulhès, 31403 Toulouse, France. E-mail: anne.lorsignol{at}toulouse.inserm.fr Abstract Glucose is known to modify electrical activity of neurons in different hypothalamic areas such as the arcuate nucleus (ARC) or the ventromedian nucleus. In these structures, it has been demonstrated that glucose-induced excitation of neurons involves ATP-sensitive K + (K ATP ) channel closure. The aim of the present study was to determine whether ARC neurons were able to detect high extracellular glucose concentrations and which mechanisms were involved in this detection by using whole-cell and cell-attached patch-clamp techniques in acute mouse brain slices. An increase from 5 to 20 mmol/l glucose stimulated 19% and inhibited 9% of ARC neurons. Because of the high-glucose concentrations used, we called these neurons high-glucose–excited (HGE) and high-glucose–inhibited (HGI) neurons, respectively. Glucose-induced depolarization of HGE neurons was not abolished by tetrodotoxin treatment and was correlated with an increase of membrane conductance that reversed at ∼20 mV. Experiments with diazoxide, pinacidil, or tolbutamide showed that K ATP channels were present and functional in most of the ARC neurons but were mostly closed at 5 mmol/l glucose. Moreover, HGE neurons were also present in ARC of Kir6.2 null mice. These results suggested that ARC neurons have the ability to sense higher glucose concentrations than 5 mmol/l through a new K ATP channel–independent mechanism. ARC, arcuate nucleus HGE, high glucose excited HGI, high glucose inhibited KATP channel, ATP-sensitive K+ channel TTX, tetrodotoxin VMH, ventromedial hypothalamus VMN, ventromedian nucleus Footnotes Accepted July 30, 2004. Received June 8, 2004. DIABETES