title: 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.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Deng
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Pang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lei
authors.forename: Sojin
authors.initials: S
authors.lastname: Shikano
authors.forename: Qiaojie
authors.initials: Q
authors.lastname: Xiong
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.forename: Barry
authors.initials: B
authors.lastname: London
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Zao C
authors.initials: ZC
authors.lastname: Xu
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051665:Kv1.4 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051665:Kv1.4 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D011493:Protein Kinase C; D011188:Potassium