2014年4月
Dysfunction of KCNK potassium channels impairs neuronal migration in the developing mouse cerebral cortex.
Cerebral cortex
- ,
- ,
- 巻
- 24
- 号
- 4
- 開始ページ
- 1017
- 終了ページ
- 1029
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/cercor/bhs387
- 出版者・発行元
- Oxford University Press
Development of the cerebral cortex depends partly on neural activity, but the identity of the ion channels that might contribute to the activity-dependent cortical development is unknown. KCNK channels are critical determinants of neuronal excitability in the mature cerebral cortex, and a member of the KCNK family, KCNK9, is responsible for a maternally transmitted mental retardation syndrome. Here, we have investigated the roles of KCNK family potassium channels in cortical development. Knockdown of KCNK2, 9, or 10 by RNAi using in utero electroporation impaired the migration of late-born cortical excitatory neurons destined to become Layer II/III neurons. The migration defect caused by KCNK9 knockdown was rescued by coexpression of RNAi-resistant functional KCNK9 mutant. Furthermore, expression of dominant-negative mutant KCNK9, responsible for the disease, and electrophysiological experiments demonstrated that ion channel function was involved in the migration defect. Calcium imaging revealed that KCNK9 knockdown or expression of dominant-negative mutant KCNK9 increased the fraction of neurons showing calcium transients and the frequency of spontaneous calcium transients. Mislocated neurons seen after KCNK9 knockdown stayed in the deep cortical layers, showing delayed morphological maturation. Taken together, our results suggest that dysfunction of KCNK9 causes a migration defect in the cortex via an activity-dependent mechanism.
- リンク情報
-
- DOI
- https://doi.org/10.1093/cercor/bhs387 本文へのリンクあり
- CiNii Articles
- http://ci.nii.ac.jp/naid/120005651926
- CiNii Books
- http://ci.nii.ac.jp/ncid/AA10777916
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000333048200016&DestApp=WOS_CPL
- URL
- http://academic.oup.com/cercor/article-pdf/24/4/1017/14100126/bhs387.pdf 本文へのリンクあり
- ID情報
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- DOI : 10.1093/cercor/bhs387
- ISSN : 1047-3211
- eISSN : 1460-2199
- CiNii Articles ID : 120005651926
- CiNii Books ID : AA10777916
- Web of Science ID : WOS:000333048200016