Up-regulation of A-type potassium currents protects neurons against cerebral ischemia |
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| Authors: | Ping Deng Zhi-Ping Pang Zhigang Lei Sojin Shikano Qiaojie Xiong Brandon K Harvey Barry London Yun Wang Min Li Zao C Xu |
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| Affiliation: | 1Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA;2Department of Neuroscience and High Throughput Biology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;3National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA;4Division of Cardiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA |
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| 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 IA against ischemia. |
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| Keywords: | excitotoxicity neuroprotection potassium channels striatum stroke |
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