Dynamic localization and clustering of dendritic KV2.1 voltage-dependent potassium, channels in developing hippocampal neurons
Dynamic localization and clustering of dendritic KV2.1 voltage-dependent potassium, channels in developing hippocampal neurons
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DOI：
10.1016/s0306-4522(01)00476-6
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Trimmer, JS
中科院分区：
文献类型：
--
作者：
Antonucci, DE;Lim, ST;Trimmer, JS
电压依赖性钾通道的高度可变的空间和时间表达模式调节树突状细胞的兴奋性。在培养的海马神经元中，体树突Kv 2.1通道是延迟整流钾电流的主要组成部分，其中Kv 2.1定位于索马和近端树突上的大簇。本研究发现，在培养的大鼠海马GABA能中间神经元和海马锥体神经元中，内源性Kv2.1的聚集存在显著差异。在锥体细胞中，该过程暂时延迟。重组绿色荧光蛋白标记的Kv2.1的定位和聚类通过相同的事件序列发生。并且活神经元中GFP-Kv 2.1簇的成像揭示了簇形成的基础的动态融合事件。GFP-Kv 2.1的过表达加速了锥体神经元中的成簇程序，从而消除了锥体神经元和中间神经元中观察到的Kv 2. 1成簇的差异。共聚焦成像显示Kv2.1与培养的神经元中的基底膜的优先关联，并且在晶体管上培养的前神经元的电生理记录显示Kv2.1贡献了先前描述的粘附连接延迟整流钾电导的大部分。最后，Kv2.1簇与Ryanodine受体胞内Ca ~（2+）（[Ca ~（2 +]（i））释放通道在空间上有关联，这些发现揭示了Kv2.1钾通道在发育过程中逐步组装成膜簇，并与Ca ~（2+）信号装置相关联。总之，这些数据表明：Kv2.1的限制性定位可能在先前观察到的该钾通道调节树突状[Ca 2 +]（i）瞬变的贡献中起重要作用。(C)2001年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Dendritic excitability is modulated by the highly variable spatial and temporal expression pattern of voltage-dependent potassium channels. Somatodendritic Kv2.1 channels contribute a major component of delayed rectifier potassium current in cultured hippocampal neurons, where Kv2.1 is localized to large clusters on the soma and proximal dendrites. Here we found that dramatic differences exist in the clustering of endogenous Kv2.1 in cultured rat hippocampal GABAergic interneurons and glutamatergic pyramidal neurons, Studies on neurons developing in culture revealed that while a similar sequence of Kv2.1 localization and clustering occurred in both cell types. the process was temporally delayed in pyramidal cells. Localization and clustering of recombinant green fluorescent protein-tagged Kv2.1 occurred by the same sequence of events. and imaging of GFP-Kv2.1 clustering in living neurons revealed dynamic fusion events that underlie cluster formation. Overexpression of GFP-Kv2.1 accelerated the clustering program in pyramidal neurons such that the observed differences in Kv2.1 clustering in pyramidal neurons and interneurons were eliminated. Confocal imaging showed a preferential association of Kv2.1 with the basal membrane in cultured neurons, and electrophysiological recordings front neurons cultured on transistors revealed that Kv2.1 contributed the bulk of a previously described adherens junction delayed rectifier potassium conductance. Finally, Kv2.1 clusters were found spatially associated with ryanodine receptor intracellular Ca2+ ([Ca2+](i)) release channels.These findings reveal a stepwise assembly of Kv2.1 potassium channels into membrane clusters during development, and an association of these clusters with Ca2+, signaling apparatus. Together these data suggest that the: restricted localization of Kv2.1 may play an important role in the previously observed contribution of this potassium channel in regulating dendritic [Ca2+](i) transients. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.