Up-Regulation of A-Type Potassium Currents Protects Neurons Against Cerebral Ischemia
| Autor: | Min Li, Zhiping P. Pang, Brandon K. Harvey, Barry London, Qiaojie Xiong, Sojin Shikano, Ping Deng, Zao C. Xu, Zhigang Lei, Yun Wang |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Programmed cell death Ischemia Excitotoxicity Striatum Biology medicine.disease_cause Neuroprotection Brain Ischemia Mice Downregulation and upregulation medicine Animals Humans Rats Wistar Protein kinase A Cells Cultured Protein Kinase C Mice Knockout Neurons Brain medicine.disease Potassium channel Rats Up-Regulation HEK293 Cells Shal Potassium Channels nervous system Neurology Potassium Channels Voltage-Gated Potassium Kv1.4 Potassium Channel Female Neurology (clinical) Cardiology and Cardiovascular Medicine Neuroscience Feature Article Commentary |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 31:1823-1835 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/jcbfm.2011.88 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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