The incretin hormone glucagon-like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage-dependent potassium channel

Abstract

The olfactory system is intricately linked with the endocrine system where it may serve as a detector of internal metabolic state or energy homeostasis in addition to its classical function as a sensor of external olfactory information. The recent development of transgenic mGLU-YFP mice that express a genetic reporter under the control of the preproglucagon reporter, suggested the presence of the gut hormone, glucagon-like peptide (GLP-1) in deep short axon cells (dSAC; Cajal cells) of the olfactory bulb and its neuromodulatory effect on the mitral cell (MC) first order neurons. A MC target for the peptide was determined using GLP-1R binding assays, immunocytochemistry for the receptor, and injection of fluorescently-labelled GLP-1 analog Exendin-4. Using patch-clamp recording of olfactory bulb slices in the whole-cell configuration, we report that GLP-1 and its stable analog Exendin-4 increase action potential (AP) firing frequency of MCs by decreasing the interburst interval rather than modifying the AP shape, train length, or interspike interval. GLP-1 decreases Kv1.3 channel contribution to outward currents in voltage-clamp recordings as determined by pharmacological block of Kv1.3 or utilizing mice with Kv1.3 gene-targeted deletion as a negative control. Because fluctuations in GLP-1 concentrations monitored by the olfactory bulb could modify firing frequency of MCs, olfactory coding could change depending upon nutritional or physiological state. As a regulator of neuronal activity, GLP-1 or its analog may be a new metabolic factor with potential therapeutic target to the olfactory bulb (i.e. intranasal delivery) to control an imbalance in energy homeostasis.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1WUu4sn
via IFTTT