Doczi Megan A, Vitzthum Carl M, Forehand Cynthia J
Norwich University, 158 Harmon Drive, Northfield, VT 05663, USA.
Norwich University, 158 Harmon Drive, Northfield, VT 05663, USA.
Neurosci Lett. 2016 Mar 11;616:182-8. doi: 10.1016/j.neulet.2016.01.068. Epub 2016 Feb 1.
Specialized hypothalamic neurons integrate the homeostatic balance between food intake and energy expenditure, processes that may become dysregulated during the development of diabetes, obesity, and other metabolic disorders. Shaker family voltage-gated potassium channels (Kv1) contribute to the maintenance of resting membrane potential, action potential characteristics, and neurotransmitter release in many populations of neurons, although hypothalamic Kv1 channel expression has been largely unexplored. Whole-cell patch clamp recordings from avian hypothalamic brain slices demonstrate a developmental shift in the electrophysiological properties of avian arcuate nucleus neurons, identifying an increase in outward ionic current that corresponds with action potential maturation. Additionally, RT-PCR experiments identified the early expression of Kv1.2, Kv1.3, and Kv1.5 mRNA in the embryonic avian hypothalamus, suggesting that these channels may underlie the electrophysiological changes observed in these neurons. Real-time quantitative PCR analysis on intact microdissections of embryonic hypothalamic tissue revealed a concomitant increase in Kv1.2 and Kv1.5 gene expression at key electrophysiological time points during development. This study is the first to demonstrate hypothalamic mRNA expression of Kv1 channels in developing avian embryos and may suggest a role for voltage-gated ion channel regulation in the physiological patterning of embryonic hypothalamic circuits governing energy homeostasis.
特化的下丘脑神经元整合食物摄入与能量消耗之间的稳态平衡,而在糖尿病、肥胖症及其他代谢紊乱的发展过程中,这些过程可能会失调。震颤家族电压门控钾通道(Kv1)有助于维持许多神经元群体的静息膜电位、动作电位特征及神经递质释放,尽管下丘脑Kv1通道的表达在很大程度上尚未得到充分研究。对鸟类下丘脑脑片进行的全细胞膜片钳记录显示,鸟类弓状核神经元的电生理特性存在发育转变,发现外向离子电流增加,这与动作电位成熟相对应。此外,逆转录-聚合酶链反应(RT-PCR)实验确定了Kv1.2、Kv1.3和Kv1.5 mRNA在胚胎期鸟类下丘脑中的早期表达,表明这些通道可能是这些神经元中观察到的电生理变化的基础。对胚胎下丘脑组织完整微切割样本进行的实时定量PCR分析显示,在发育过程中的关键电生理时间点,Kv1.2和Kv1.5基因表达同时增加。本研究首次证明了发育中的鸟类胚胎下丘脑中Kv1通道的mRNA表达,并可能提示电压门控离子通道调节在控制能量稳态的胚胎下丘脑回路生理模式形成中的作用。