The transient K+ current (IA) carried by pore forming Kv4.2 subunits regulates the propagation of synaptic input, dendritic excitability, and synaptic plasticity in CA1 pyramidal neuron dendrites of the hippocampus. We report that the Ca2+ channel subunit Cav2.3 regulates IA in this cell type. We first identified Cav2.3 as a Kv4.2 interacting protein in a proteomic screen and we confirmed Cav2.3-Kv4.2 complex association using multiple techniques. Functionally, Cav2.3 Ca2+-entry increases Kv4.2-mediated whole-cell current due to an increase in Kv4.2 surface expression. Using pharmacology and Cav2.3 knockout mice, Cav2.3 was found to promote whole-cell IA and the increasing gradient of IA in the apical dendrite distal to the neuronal soma. Furthermore, the loss of Cav2.3 function leads to enhancement of synaptic currents and spine Ca2+ influx. These results present Cav2.3 and Kv4.2 as integral constituents of an ion channel complex that impacts synaptic function in the hippocampus.

中文翻译：

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R型电压门控Ca2+通道介导海马树突突触输入的A型K+电流调节

由孔形成 Kv4.2 亚基携带的瞬态 K+ 电流 (IA) 调节海马 CA1 锥体神经元树突中突触输入、树突兴奋性和突触可塑性的传播。我们报告 Ca2+ 通道亚基 Cav2.3 在这种细胞类型中调节 IA。我们首先在蛋白质组学筛选中将 Cav2.3 鉴定为 Kv4.2 相互作用蛋白，并使用多种技术确认了 Cav2.3-Kv4.2 复合物关联。在功能上，由于 Kv4.2 表面表达的增加，Cav2.3 Ca2+ 进入增加了 Kv4.2 介导的全细胞电流。使用药理学和 Cav2.3 基因敲除小鼠，发现 Cav2.3 可促进全细胞 IA 和神经元胞体远端顶端树突中 IA 的梯度增加。此外，Cav2.3 功能的丧失导致突触电流和脊柱 Ca2+ 流入的增强。