A new ATP-sensitive K+ channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus
Diabetes. 2004-10-25; 53(11): 2767-2775
DOI: 10.2337/diabetes.53.11.2767
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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 approximately 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.