Synaptic Structure Laboratory, Instituto de Investigación en Discapacidades Neurológicas (IDINE), Dept. Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, Campus Biosanitario, C/Almansa 14, 02008 Albacete, Spain.
Int J Mol Sci. 2019 Jan 9;20(2):246. doi: 10.3390/ijms20020246.
The Kv4 family of voltage-gated K⁺ channels underlie the fast transient (A-type) outward K⁺ current. Although A-type currents are critical to determine somato-dendritic integration in central neurons, relatively little is known about the precise subcellular localisation of the underlying channels in hippocampal circuits. Using histoblot and immunoelectron microscopic techniques, we investigated the expression, regional distribution and subcellular localisation of Kv4.2 and Kv4.3 in the adult brain, as well as the ontogeny of their expression during postnatal development. Histoblot demonstrated that Kv4.2 and Kv4.3 proteins were widely expressed in the brain, with mostly non-overlapping patterns. During development, levels of Kv4.2 and Kv4.3 increased with age but showed marked region- and developmental stage-specific differences. Immunoelectron microscopy showed that labelling for Kv4.2 and Kv4.3 was differentially present in somato-dendritic domains of hippocampal principal cells and interneurons, including the synaptic specialisation. Quantitative analyses indicated that most immunoparticles for Kv4.2 and Kv4.3 were associated with the plasma membrane in dendritic spines and shafts, and that the two channels showed very similar distribution patterns in spines of principal cells and along the surface of granule cells. Our data shed new light on the subcellular localisation of Kv4 channels and provide evidence for their non-uniform distribution over the plasma membrane of hippocampal neurons.
电压门控钾离子通道 Kv4 家族是快速瞬态（A 型）外向钾离子电流的基础。尽管 A 型电流对于确定中枢神经元的体树突整合至关重要，但对于海马回路中基础通道的确切亚细胞定位相对知之甚少。使用组织印迹和免疫电子显微镜技术，我们研究了 Kv4.2 和 Kv4.3 在成年脑中的表达、区域分布和亚细胞定位，以及它们在出生后发育过程中的表达的发育变化。组织印迹表明 Kv4.2 和 Kv4.3 蛋白在脑中广泛表达，且表达模式大多不重叠。在发育过程中，Kv4.2 和 Kv4.3 的水平随年龄增长而增加，但表现出明显的区域和发育阶段特异性差异。免疫电子显微镜显示，Kv4.2 和 Kv4.3 的标记在海马主细胞和中间神经元的体树突域中存在差异，包括突触特化。定量分析表明，大多数 Kv4.2 和 Kv4.3 的免疫颗粒与树突棘和轴突中的质膜相关，并且这两个通道在主细胞的棘突中和颗粒细胞表面上表现出非常相似的分布模式。我们的数据为 Kv4 通道的亚细胞定位提供了新的见解，并为它们在海马神经元质膜上的非均匀分布提供了证据。
