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Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel

Title: Mitochondrial Ultrastructure And Glucose Signaling Pathways Attributed To The Kv1.3 Ion Channel.
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Name(s): Kovach, Christopher P., author
Al Koborssy, Dolly, author
Huang, Zhenbo, author
Chelette, Brandon M., author
Fadool, James M., author
Fadool, Debra A., author
Type of Resource: text
Genre: Text
Date Issued: 2016-05-19
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Gene-targeted deletion of the potassium channel Kv1.3 (Kv1.3(-/-)) results in "Super-smeller" mice with a sensory phenotype that includes an increased olfactory ability linked to changes in olfactory circuitry, increased abundance of olfactory cilia, and increased expression of odorant receptors and the G-protein, G(olf). Kv1.3(-/-) mice also have a metabolic phenotype including lower body weight and decreased adiposity, increased total energy expenditure (TEE), increased locomotor activity, and resistance to both diet- and genetic-induced obesity. We explored two cellular aspects to elucidate the mechanism by which loss of Kv1.3 channel in the olfactory bulb (OB) may enhance glucose utilization and metabolic rate. First, using in situ hybridization we find that Kv1.3 and the insulin-dependent glucose transporter type 4 (GLUT4) are co-localized to the mitral cell layer of the OB. Disruption of Kv1.3 conduction via construction of a pore mutation (W386F Kv1.3) was sufficient to independently translocate GLUT4 to the plasma membrane in HEK 293 cells. Because olfactory sensory perception and the maintenance of action potential (AP) firing frequency by mitral cells of the OB is highly energy demanding and Kv1.3 is also expressed in mitochondria, we next explored the structure of this organelle in mitral cells. We challenged wildtype (WT) and Kv1.3(-/-) male mice with a moderately high-fat diet (MHF, 31.8 % kcal fat) for 4 months and then examined OB ultrastructure using transmission electron microscopy. In WT mice, mitochondria were significantly enlarged following diet-induced obesity (DIO) and there were fewer mitochondria, likely due to mitophagy. Interestingly, mitochondria were significantly smaller in Kv1.3(-/-) mice compared with that of WT mice. Similar to their metabolic resistance to DIO, the Kv1.3(-/-) mice had unchanged mitochondria in terms of cross sectional area and abundance following a challenge with modified diet. We are very interested to understand how targeted disruption of the Kv1.3 channel in the OB can modify TEE. Our study demonstrates that Kv1.3 regulates mitochondrial structure and alters glucose utilization; two important metabolic changes that could drive whole system changes in metabolism initiated at the OB.
Identifier: FSU_libsubv1_wos_000376059000001 (IID), 10.3389/fphys.2016.00178 (DOI)
Keywords: brain insulin, diet-induced obesity, gated potassium channel, glucose transporter, hexose transporter, insulin-resistance, in-vivo, k+ channels, mitochondria, mouse-brain, olfactory bulb, olfactory-bulb, permeability transition, potassium channel, tyrosine phosphorylation
Publication Note: The publisher’s version of record is available at https://doi.org/10.3389/fphys.2016.00178
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000376059000001
Owner Institution: FSU
Is Part Of: Frontiers in Physiology.
1664-042X
Issue: vol. 7

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Kovach, C. P., Al Koborssy, D., Huang, Z., Chelette, B. M., Fadool, J. M., & Fadool, D. A. (2016). Mitochondrial Ultrastructure And Glucose Signaling Pathways Attributed To The Kv1.3 Ion Channel. Frontiers In Physiology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000376059000001