@misc{oai:ir.soken.ac.jp:00001116,
 author = {柴崎, 貢志 and シバサキ, コウジ and SHIBASAKI, Koji},
 month = {2016-02-17},
 note = {Neurons express variety of ion channel genes to exert their diverse activity. Each gene product localizes at specific subcellular compartment. This targeted localization of ion channels is indispensable for the channels to function properly. In this study, I focused on Kv4.2 voltage- gated K+ channel and investigated how the localization of this channel was regulated in cerebellar granule neurons. Kv4.2 channel in vivo is found in glomeruli, where the dendrites of the cells and mossy fibers form synapses. However, immunocytochemical staining of the cultured granule cells showed that the localization of Kv4.2 was restricted to the cell body. I hypothesized that this was due to the lack of proper triggering signal possibly provided by the excitatory synaptic input from mossy fibers. Thus I developed a co-culture with pontine gray nucleus, an origin of mossy fiber and asked whether the Kv4.2 channels resumed their normal localization. In the new co- culture system, mossy fiber formed large synapsin-I positive clusters appeared on the mossy fiber, which were associated with PSD-95 on granule cell dendrites. The synapse-like structures were formed between the mossy fibers and the granule cell dendrites. Kv4.2 was co-localized with this structure. Therefore, contacts with mossy fibers induced targeting of the Kv4.2 channels from soma to dendrites and synapses in the granule cells. Treatment of the culture with presynaptic exocytosis inhibitors, tetrodotoxin, ω-conotoxin GVIA, or botulinum A toxin, disrupted the clustering of Kv4.2 at the synapse-like structure. Interestingly, mossy fiber contacts induced synaptic targeting of both Kv4.2 and NR1 that was a NMDA receptor subunit. The synaptic localization of Kv4.2 was regulated by the activation of NMDA- and/or AMPA-receptors, while activity blockage increased synaptic targeting of the NR1 subunit. These results indicate that the synaptic targeting of the two channels/receptors is regulated in a contradictory manner by the activity. This differential regulation ensures effective changes in synaptic excitability and should be involved in synaptic maturation as well as in synaptic plasticity., 総研大甲第560号},
 title = {Mossy Fiber Contacts Trigger the Localization of Kv4.2to Dendrites and Synapses in Developing CerebellarGranule Neurons},
 year = {}
}