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

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 (I(A)) 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 I(A) 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 I(A) 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 I(A) 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.

• Authors: Ping Deng, Zhi-Ping Pang, Zhigang Lei, Sojin Shikano, Qiaojie Xiong, Brandon K Harvey, Barry London, Yun Wang, Min Li, Zao C Xu
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 31 Issue 9 Pg. 1823-35 (Sep 2011) ISSN: 1559-7016 [Electronic] United States
• PMID: 21673715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Kv1.4 Potassium Channel
• Potassium Channels, Voltage-Gated
• Shal Potassium Channels
• Protein Kinase C
• Potassium

Topics

• Animals
• Brain (cytology, metabolism, pathology)
• Brain Ischemia (genetics, metabolism, pathology)
• Cells, Cultured
• Female
• HEK293 Cells
• Humans
• Kv1.4 Potassium Channel (genetics, metabolism)
• Male
• Mice
• Mice, Knockout
• Neurons (cytology, metabolism, pathology)
• Potassium (metabolism)
• Potassium Channels, Voltage-Gated (genetics, metabolism)
• Protein Kinase C (metabolism)
• Rats
• Rats, Wistar
• Shal Potassium Channels (genetics, metabolism)
• Up-Regulation