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Na(+)/Ca(2+) exchanger 2 is neuroprotective by exporting Ca(2+) during a transient focal cerebral ischemia in the mouse

Cited 45 time in Web of Science Cited 43 time in Scopus
Authors
Jeon, Daejong; Chu, Kon; Jung, Keun-Hwa; Kim, Manho; Yoon, Byung-Woo; Lee, C Justin; Oh, Uhtaek; Shin, Hee-Sup
Issue Date
2008
Publisher
Elsevier
Citation
Cell Calcium. 43 (2008) 482-491
Keywords
AnimalsBiological TransportBrain/physiopathologyCalcium/*metabolismCell SurvivalCerebral Infarction/pathologyIschemic Attack, Transient/*metabolism/pathology/physiopathologyMembrane PotentialsMiceMice, KnockoutNeurons/pathologyNeuroprotective Agents/metabolismPatch-Clamp TechniquesSodium-Calcium Exchanger/genetics/metabolism/*physiology
Abstract
Na(+)/Ca(2+) exchanger (NCX), by mediating Na(+) and Ca(2+) fluxes bi-directionally, assumes a role in controlling the Ca(2+) homeostasis in the ischemic brain. It has been suggested that the three isoforms of NCX (NCX1, 2 and 3) may be differentially involved in permanent cerebral ischemia. However, the role of NCX2 has not been defined in ischemic reperfusion injury after a transient focal cerebral ischemia. Furthermore, it is not known whether NCX2 imports or exports intracellular Ca(2+) ([Ca(2+)](i)) following ischemia and reperfusion. To define the role of NCX2 in ischemia and reperfusion, we examined mice lacking NCX2, in vivo and in vitro. After an in vitro ischemia, a significantly slower recovery in population spike amplitudes, a sustained elevation of [Ca(2+)](i) and an increased membrane depolarization were developed in the NCX2-deficient hippocampus. Moreover, a transient focal cerebral ischemia in vivo produced a larger infarction and more cell death in the NCX2-deficient mouse brain. In particular, in the wild type brain, NCX2-expressing neurons were largely spared from cell death after ischemia. Our results suggest that NCX2 exports Ca(2+) in ischemia and thus protects neuronal cells from death by reducing [Ca(2+)](i) in the adult mouse brain.
ISSN
0143-4160 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17884163

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WCC-4PPFTBF-1-F&_cdi=6735&_user=168665&_orig=search&_coverDate=05%2F31%2F2008&_sk=999569994&view=c&wchp=dGLbVlW-zSkWb&md5=50914fe03e5572d1163b720670049456&ie=/sdarticle.pdf

http://hdl.handle.net/10371/68170
DOI
https://doi.org/10.1016/j.ceca.2007.08.003
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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