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Key points

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    Potassium ion channels dampen excitability of neurons but may also be sensors of internal metabolism.
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    Mice with gene-targeted deletion of the potassium channel Kv1.3, a channel regulating action potential spike frequency in the olfactory bulb, are ‘super-smellers’ and resistant to diet-induced obesity.
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    Electrophysiology experiments demonstrate that Kv1.3 is sensitive to the active form of glucose and that Kv1.3-expressing mitral neurons of the olfactory bulb are predominantly inhibited by a change to high glucose concentration.
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    Modulation of the neuron target properties of spike firing rather than action potential shape involves synaptic activity of glutamate or GABA signalling circuits, and is dependent upon Kv1.3 expression.
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    Given the rising incidence of metabolic disorders attributed to weight gain, changes in neuronal excitability in brain regions regulating sensory perception of food are of consequence if we are to understand the function of the brain under chronic hyperglycaemia as is typical with obesity.

Abstract  The olfactory bulb has recently been proposed to serve as a metabolic sensor of internal chemistry, particularly that modified by metabolism. Because the voltage-dependent potassium channel Kv1.3 regulates a large proportion of the outward current in olfactory bulb neurons and gene-targeted deletion of the protein produces a phenotype of resistance to diet-induced obesity in mice, we hypothesized that this channel may play a role in translating energy availability into a metabolic signal. Here we explored the ability of extracellular glucose concentration to modify evoked excitability of the mitral neurons that principally regulate olfactory coding and processing of olfactory information. Using voltage-clamp electrophysiology of heterologously expressed Kv1.3 channels in HEK 293 cells, we found that Kv1.3 macroscopic currents responded to metabolically active (d-) rather than inactive (l-) glucose with a response profile that followed a bell-shaped curve. Olfactory bulb slices stimulated with varying glucose concentrations showed glucose-dependent mitral cell excitability as evaluated by current-clamp electrophysiology. While glucose could be either excitatory or inhibitory, the majority of the sampled neurons displayed a decreased firing frequency in response to elevated glucose concentration that was linked to increased latency to first spike and decreased action potential cluster length. Unlike modulation attributed to phosphorylation, glucose modulation of mitral cells was rapid, less than one minute, and was reversible within the time course of a patch recording. Moreover, we report that modulation targets properties of spike firing rather than action potential shape, involves synaptic activity of glutamate or GABA signalling circuits, and is dependent upon Kv1.3 expression. Given the rising incidence of metabolic disorders attributed to weight gain, changes in neuronal excitability in brain regions regulating sensory perception of food are of consequence.