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Developmental Localization of the Kv1.3 Voltage‐gated Potassium Channel and Insulin Receptor in Hypothalamic Nuclei Governing Energy Homeostasis
Author(s) -
Doczi Megan Anne,
Yacawych Warren
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb46
Subject(s) - energy homeostasis , medicine , endocrinology , biology , hypothalamus , arcuate nucleus , insulin , insulin receptor , homeostasis , glucose homeostasis , potassium channel , microbiology and biotechnology , insulin resistance , obesity
The Kv1.3 voltage‐gated potassium channel is expressed in various cell types associated with metabolic function including skeletal muscle, adipocytes, and neurons. Pharmacological Kv1.3 blockade has been shown to profoundly affect the regulation of body weight and energy homeostasis, suggesting that this channel may play a key role in regulating metabolic processes. In addition, the insulin hormone can suppress Kv1.3 ionic current through the tyrosine kinase activity of the insulin receptor (IR), suggesting a link between insulin signaling and Kv1.3 channel activity. Recent evidence from our laboratory has identified Kv1.3 gene expression in the embryonic avian hypothalamus, a brain region critical for maintaining metabolic homeostasis, although the specific protein localization remains unclear. The purpose of this study was to identify the localization of Kv1.3 and IR in the developing embryonic avian hypothalamus to establish a future model for in ovo insulin delivery, ultimately determining whether insulin affects the expression and function of Kv1.3 during development. Western blot analysis was used to validate monoclonal antibody binding for both the Kv1.3 channel and IR in embryonic day 12 (E12) avian whole brain lysates (n = 3). In accordance with the observed insulin‐dependent current suppression of the channel, we tested the hypothesis that Kv1.3 is localized to hypothalamic nuclei governing food intake and energy expenditure. Immunohistochemical analysis of hypothalamic brain sections from E12 embryos indicate that IR protein is localized to the ventromedial hypothalamus and arcuate nucleus (n = 3), while Kv1.3 channels are expressed more widely throughout this brain region, including enhanced staining within the subventricular zone (n = 3). This study demonstrates the hypothalamic expression of both Kv1.3 and IR in the developing avian embryo and suggests a role for voltage‐gated ion channel regulation in the physiological patterning of embryonic hypothalamic circuits. Further understanding the localization and function of insulin‐sensitive Kv1.3 channels during hypothalamic embryogenesis may provide insight into the developmental mechanisms of metabolic disorders such as diabetes and obesity. Support or Funding Information Support made possible by the Vermont Genetics Network through Grant Number P20GM103449 from the INBRE Program of the National Institute of General Medical Sciences (NIGMS) and the National Center for Research Resources (NCRR), components of the National Institutes of Health (NIH).