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Supersmellers, Obesity, and Neural Circuits - Discovered roles of Potassium Ion Channels Beyond the Resting Potential| old_uid | 3954 |
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| title | Supersmellers, Obesity, and Neural Circuits - Discovered roles of Potassium Ion Channels Beyond the Resting Potential |
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| start_date | 2008/01/29 |
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| schedule | 10h-11h30 |
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| online | no |
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| location_info | amphi G1 |
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| summary | The primary role of voltage-gated ion channels is to conduct charged species through a vestibule to establish an electrical signal. In addition to their well-described roles in regulating excitability, we now know that ion channels are not passive elements, but can directly control intracellular biochemical events such as gene expression, activation of enzymatic cascades, or regulation of the cell cycle. Our laboratory studies a voltage-gated ion channel from the Shaker subfamily, Kv1.3, which acts to dampen excitability of mitral cell neurons in the olfactory bulb. Through gene-targeted deletion of Kv1.3 we have uncovered non-traditional roles in potassium channels while phenotypically characterizing loss of function in the mice - from behavior up through electrical excitability in the olfactory bulb. Experiments will be presented that describe our use of olfactory threshold and discrimination paradigms, object memory recognition tests, protein biochemistry, whole-cell electrophysiology, metabolic chambers, and genetically- engineered reporter genes that were used to characterize the Kv1.3-null mice. Three principle phenotypes will be described in depth: 1) Increased threshold and discrimination of the Kv1.3-null, “Super-smeller” mice, 2) Low body weight and resistance to diet- or genetically-induced obesity in a Kv1.3-deficient background, and 3) Supernumerary glomeruli and altered axonal circuitry generated via modified action potential frequency in the mitral cell neurons of the Kv1.3-null mice. These data indicate unsuspected roles for potassium ion channels that include neuronal proliferation, olfactory coding, energy homeostasis, and circuitry formation. We are currently exploring putative mechanisms for these non-traditional roles and data will be presented that suggest Kv1.3 deletion abrogates obesity via increased locomotor activity and mass-specific metabolism. Additionally we have optimize a novel technique called intranasal insulin delivery to demonstrate that insulin-induced phosphorylation of Kv1.3 in the olfactory bulb suppresses channel current and replicates a “Super-smeller” behavioral phenotype. |
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| responsibles | Gervais |
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