<学術雑誌論文>
Reduction of KCC2 Expression and GABAA Receptor-Mediated Excitation after In Vivo Axonal Injury

作成者
本文言語
出版者
発行日
雑誌名
開始ページ
終了ページ
出版タイプ
アクセス権
概要 After axotomy, application of muscimol, a GABAA receptor agonist, induced an increase in intracellular Ca2+ ([Ca2+]i) in dorsal motor neurons of the vagus (DMV neurons). Elevation of [Ca2+]i by muscim...ol was blocked by bicuculline, tetrodotoxin, and Ni2+. In axotomized DMV neurons measured with gramicidin perforated-patch recordings, reversal potentials of the GABAA receptor-mediated response, presumably equal to the equilibrium potential of Cl-, were more depolarized than that in intact neurons. Thus, GABAA receptor-mediated excitation is suggested to be attributable to Cl- efflux out of the cell because of increased intracellular Cl- concentration ([Cl-]i) in axotomized neurons. Regulation of [Cl-]i in both control and injured neurons was disturbed by furosemide and bumetanide and by manipulating cation balance across the membrane, suggesting that functional alteration of furosemide-sensitive cation-Cl- cotransporters is responsible for the increase of [Cl-]i after axotomy. In situ hybridization revealed that neuron-specific K+-Cl- cotransporter (KCC2) mRNA was significantly reduced in the DMV after axotomy compared with that in control neurons. Similar expression of Na+, K+-Cl- cotransporter mRNA was observed between axotomized and control DMV neurons. Thus, axotomy led to disruption of [Cl-]i regulation attributable to a decrease of KCC2 expression, elevation of intracellular Cl-, and an excitatory response to GABA. A switch of GABA action from inhibitory to excitatory might be a mechanism contributing to excitotoxicity in injured neurons.続きを見る

本文情報を非表示

55 pdf 302 KB 107  

詳細

レコードID
査読有無
権利関係
関連情報
主題
ISSN
NCID
タイプ
登録日 2009.04.22
更新日 2017.02.08