Department of Psychiatry and Behavioral Sciences, Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 300329, USA.
Neuroscience. 2010 Dec 15;171(3):721-33. doi: 10.1016/j.neuroscience.2010.09.011. Epub 2010 Sep 16.
The Kv4 potassium channel α subunits, Kv4.1, Kv4.2, and Kv4.3, determine some of the fundamental physiological properties of neurons in the CNS. Kv4 subunits are associated with auxiliary β-subunits, such as the potassium channel interacting proteins (KChIP1 - 4), which are thought to regulate the trafficking and gating of native Kv4 potassium channels. Intriguingly, KChIP1 is thought to show cell type-selective expression in GABA-ergic inhibitory interneurons, while other β-subunits (KChIP2-4) are associated with principal glutamatergic neurons. However, nothing is known about the expression of Kv4 family α- and β-subunits in specific interneurons populations in the BLA. Here, we have used immunofluorescence, co-immunoprecipitation, and Western Blotting to determine the relative expression of KChIP1 in the different interneuron subtypes within the BLA, and its co-localization with one or more of the Kv4 α subunits. We show that all three α-subunits of Kv4 potassium channel are found in rat BLA neurons, and that the immunoreactivity of KChIP1 closely resembles that of Kv4.3. Indeed, Kv4.3 showed almost complete co-localization with KChIP1 in the soma and dendrites of a distinct subpopulation of BLA neurons. Dual-immunofluorescence studies revealed this to be in BLA interneurons immunoreactive for parvalbumin, cholecystokin-8, and somatostatin. Finally, co-immunoprecipitation studies showed that KChIP1 was associated with all three Kv4 α subunits. Together our results suggest that KChIP1 is selectively expressed in BLA interneurons where it may function to regulate the activity of A-type potassium channels. Hence, KChIP1 might be considered as a cell type-specific regulator of GABAergic inhibitory circuits in the BLA.
Kv4 钾通道 α 亚基（Kv4.1、Kv4.2 和 Kv4.3）决定了中枢神经系统神经元的一些基本生理特性。Kv4 亚基与辅助 β 亚基（如钾通道相互作用蛋白（KChIP1-4））相关，后者被认为调节天然 Kv4 钾通道的运输和门控。有趣的是，KChIP1 被认为在 GABA 能抑制性中间神经元中表现出细胞类型选择性表达，而其他 β 亚基（KChIP2-4）与主要谷氨酸能神经元相关。然而，目前尚不清楚 Kv4 家族 α 和 β 亚基在 BLA 中的特定中间神经元群体中的表达情况。在这里，我们使用免疫荧光、共免疫沉淀和 Western Blotting 来确定 KChIP1 在 BLA 不同中间神经元亚型中的相对表达，并确定其与一个或多个 Kv4 α 亚基的共定位。我们表明，Kv4 钾通道的所有三个 α 亚基都存在于大鼠 BLA 神经元中，并且 KChIP1 的免疫反应性与 Kv4.3 非常相似。事实上，Kv4.3 在 BLA 神经元的体和树突中与 KChIP1 几乎完全共定位，这是 BLA 中间神经元的一个独特亚群。双免疫荧光研究表明，这些中间神经元对 parvalbumin、胆囊收缩素-8 和 somatostatin 呈免疫反应性。最后，共免疫沉淀研究表明 KChIP1 与所有三个 Kv4 α 亚基相关。我们的研究结果表明，KChIP1 在 BLA 中间神经元中选择性表达，在这些神经元中，它可能发挥作用以调节 A 型钾通道的活性。因此，KChIP1 可能被认为是 BLA 中 GABA 能抑制性回路的细胞类型特异性调节剂。
