Glucose sensitivity of mouse olfactory bulb neurons is conveyed by a voltage-gated potassium channel

Kristal Raylone Tucker, Sukhee Cho, Nicolas Thiebaud, Michael X. Henderson, Debra Ann Fadool

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2541-2561
Number of pages21
JournalJournal of Physiology
Volume591
Issue number10
DOIs
StatePublished - May 1 2013

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Voltage-Gated Potassium Channels
Olfactory Bulb
Neurons
Glucose
Electrophysiology
Action Potentials
Kv1.3 Potassium Channel
Aptitude
HEK293 Cells
Gene Deletion
Automatic Data Processing
gamma-Aminobutyric Acid
Weight Gain
Glutamic Acid
Obesity
Phosphorylation
Diet
Phenotype
Food
Incidence

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Tucker, Kristal Raylone ; Cho, Sukhee ; Thiebaud, Nicolas ; Henderson, Michael X. ; Fadool, Debra Ann. / Glucose sensitivity of mouse olfactory bulb neurons is conveyed by a voltage-gated potassium channel. In: Journal of Physiology. 2013 ; Vol. 591, No. 10. pp. 2541-2561.
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Glucose sensitivity of mouse olfactory bulb neurons is conveyed by a voltage-gated potassium channel. / Tucker, Kristal Raylone; Cho, Sukhee; Thiebaud, Nicolas; Henderson, Michael X.; Fadool, Debra Ann.

In: Journal of Physiology, Vol. 591, No. 10, 01.05.2013, p. 2541-2561.

Research output: Contribution to journalArticle

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