Alterations of A-type potassium channels in hippocampal neurons after traumatic brain injury

Zhigang Lei, Ping Deng, Jinqing Li, Zao C. Xu

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Traumatic brain injury (TBI) is associated with cognitive deficits, memory impairment, and epilepsy. Previous studies have reported neuronal loss and neuronal hyperexcitability in the post-traumatic hippocampus. A-type K + currents (I A) play a critical role in modulating the intrinsic membrane excitability of hippocampal neurons. The disruption of I A is reportedly linked to hippocampal dysfunction. The present study investigates the changes of I A in the hippocampus after TBI. TBI in rats was induced by controlled cortical impact. The impact induced a reproducible lesion in the cortex and an obvious neuronal death in the ipsilateral hippocampus CA3 region. At one week after TBI, immunohistochemical staining and Western blotting showed that the expression of I A channel subunit Kv4.2 was markedly decreased in the ipsilateral hippocampus, but remained unchanged in the contralateral hippocampus. Meanwhile, electrophysiological recording showed that I A currents in ipsilateral CA1 pyramidal neurons were significantly reduced, which was associated with an increased neuronal excitability. Furthermore, there was an increased sensitivity to bicuculline-induced seizures in TBI rats. At 8 weeks after TBI, immunohistochemical staining and electrophysiological recording indicated that I A returned to control levels. These findings suggest that TBI causes a transient downregulation of I A in hippocampal CA1 neurons, which might be associated with the hyperexcitability in the post-traumatic hippocampus, and in turn leads to seizures and epilepsy.

Original languageEnglish (US)
Pages (from-to)235-245
Number of pages11
JournalJournal of neurotrauma
Volume29
Issue number2
DOIs
StatePublished - Jan 20 2012

Keywords

  • controlled cortical impact
  • hyperexcitability
  • IA
  • K 4.2
  • Kv4.3
  • post-traumatic epilepsy

ASJC Scopus subject areas

  • Clinical Neurology

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