Up-regulation of A-type potassium currents protects neurons against cerebral ischemia

Ping Deng, Zhi Ping Pang, Zhigang Lei, Sojin Shikano, Qiaojie Xiong, Brandon K. Harvey, Barry London, Yun Wang, Min Li, Zao C. Xu

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Excitotoxicity is the major cause of many neurologic disorders including stroke. Potassium currents modulate neuronal excitability and therefore influence the pathological process. A-type potassium current (IA) is one of the major voltage-dependent potassium currents, yet its roles in excitotoxic cell death are not well understood. We report that, following ischemic insults, the IA increases significantly in large aspiny (LA) neurons but not medium spiny (MS) neurons in the striatum, which correlates with the higher resistance of LA neurons to ischemia. Activation of protein kinase Cα increases IA in LA neurons after ischemia. Cultured neurons from transgenic mice lacking both Kv1.4 and Kv4.2 subunits exhibit an increased vulnerability to ischemic insults. Increase of IA by recombinant expression of Kv1.4 or Kv4.2 is sufficient in improving the survival of MS neurons against ischemic insults both in vitro and in vivo. These results, taken together, provide compelling evidence for a protective role of I A against ischemia.

Original languageEnglish (US)
Pages (from-to)1823-1835
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • Excitotoxicity
  • neuroprotection
  • potassium channels
  • striatum
  • stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

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