Mossy fibre contact triggers the targeting of Kv4.2 potassium channels to dendrites and synapses in developing cerebellar granule neurons
Mossy fibre contact triggers the targeting of Kv4.2 potassium channels to dendrites and synapses in developing cerebellar granule neurons
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DOI：
10.1111/j.1471-4159.2004.02368.x
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发表时间：
2004-05
影响因子：
4.7
通讯作者：
K. Shibasaki;K. Nakahira;J. Trimmer;R. Shibata;Masumi Akita;Shu-ichi Watanabe;K. Ikenaka
中科院分区：
文献类型：
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作者：
K. Shibasaki;K. Nakahira;J. Trimmer;R. Shibata;Masumi Akita;Shu-ichi Watanabe;K. Ikenaka
神经元功能的区室化是通过离散亚细胞膜域中离子通道的高度局部聚集来实现的。电压门控钾 (Kv) 通道表现出高度可变的细胞和亚细胞表达模式。在这里，我们描述了小脑颗粒细胞（GC）中 Kv4.2（一种树突状 Kv 通道）的新型活动依赖性突触靶向。在体内，Kv4.2 通道在小脑肾小球中高度表达，小脑肾小球是与苔藓纤维形成突触的 GC 树突的特化。相比之下，在培养的GC中，Kv4.2被发现定位于细胞体而不是树突。为了研究突触接触的作用，我们开发了一种与来自脑桥灰核（苔藓纤维的起源）的细胞共培养的系统。在这些共培养物中，形成了突触结构，并且 Kv4.2 现在以依赖于突触活动的方式靶向这些突触位点。 NMDA 和/或 AMPA 型谷氨酸受体的激活对于共培养物中 Kv4.2 的靶向是必要的，并且在 GC 单一培养物中这些受体系统的激活在没有突触形成的情况下诱导 Kv4.2 的树突靶向。这些结果表明 Kv4.2 通道的正确靶向是由突触活动动态调节的。 Kv4.2 定位的这种活动依赖性调节在突触活动和树突兴奋性之间提供了至关重要的动态联系。
Compartmentalization of neuronal function is achieved by highly localized clustering of ion channels in discrete subcellular membrane domains. Voltage‐gated potassium (Kv) channels exhibit highly variable cellular and subcellular patterns of expression. Here, we describe novel activity‐dependent synaptic targeting of Kv4.2, a dendritic Kv channel, in cerebellar granule cells (GCs). In vivo, Kv4.2 channels are highly expressed in cerebellar glomeruli, specializations of GC dendrites that form synapses with mossy fibres. In contrast, in cultured GCs, Kv4.2 was found localized, not to dendrites but to cell bodies. To investigate the role of synaptic contacts, we developed a co‐culture system with cells from pontine grey nucleus, the origin of mossy fibres. In these co‐cultures, synaptic structures formed, and Kv4.2 was now targeted to these synaptic sites in a manner dependent on synaptic activity. Activation of NMDA‐ and/or AMPA‐type glutamate receptors was necessary for the targeting of Kv4.2 in co‐cultures, and activation of these receptor systems in GC monocultures induced dendritic targeting of Kv4.2 in the absence of synapse formation. These results indicate that the proper targeting of Kv4.2 channels is dynamically regulated by synaptic activity. This activity‐dependent regulation of Kv4.2 localization provides a crucial yet dynamic link between synaptic activity and dendritic excitability.