title: Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury.
abstract: Acidosis in the brain plays a critical role in neuronal injury in neurological diseases, including brain ischemia. One key mediator of acidosis-induced neuronal injury is the acid-sensing ion channels (ASICs). Current literature has focused on ASIC1a when studying acid signaling. The importance of ASIC2, which is also widely expressed in the brain, has not been appreciated. We found here a region-specific effect of ASIC2 on acid-mediated responses. Deleting ASIC2 reduced acid-activated current in cortical and striatal neurons, but had no significant effect in cerebellar granule neurons. In addition, we demonstrated that ASIC2 was important for ASIC1a expression, and that ASIC2a but not 2b facilitated ASIC1a surface trafficking in the brain. Further, we showed that ASIC2 deletion attenuated acidosis/ischemia-induced neuronal injury in organotypic hippocampal slices but had no effect in organotypic cerebellar slices. Consistent with an injurious role of ASIC2, we showed that ASIC2 deletion significantly protected the mouse brain from ischemic damage in vivo. These data suggest a critical region-specific contribution of ASIC2 to neuronal injury and reveal an important functional difference between ASIC2a and 2b in the brain.
authors: 1 Department of Physiology and Cell Biology, University of South Alabama, Mobile, USA.|2 School of Life Sciences, Shanghai University, Shanghai, China.
authors: Nan
authors: N
authors: Jiang
authors: 1 Department of Physiology and Cell Biology, University of South Alabama, Mobile, USA.|3 China State Institute of Pharmaceutical Industry, Shanghai, China.
authors: Junjun
authors: J
authors: Wu
authors: 4 Department of Neurobiology, Morehouse School of Medicine, Atlanta, USA.
authors: Tiandong
authors: T
authors: Leng
authors: 4 Department of Neurobiology, Morehouse School of Medicine, Atlanta, USA.
authors: Tao
authors: T
authors: Yang
authors: 1 Department of Physiology and Cell Biology, University of South Alabama, Mobile, USA.
authors: Yufan
authors: Y
authors: Zhou
authors: 5 Department of Basic Medical Science, University of Missouri-Kansas City, Kansas City, USA.
authors: Qian
authors: Q
authors: Jiang
authors: 6 Department of Mathematics and Statistics, University of South Alabama, Mobile, USA.
authors: Bin
authors: B
authors: Wang
authors: 3 China State Institute of Pharmaceutical Industry, Shanghai, China.
authors: Youjia
authors: Y
authors: Hu
authors: 2 School of Life Sciences, Shanghai University, Shanghai, China.
authors: Yong-Hua
authors: YH
authors: Ji
authors: 4 Department of Neurobiology, Morehouse School of Medicine, Atlanta, USA.
authors: Roger P
authors: RP
authors: Simon
authors: 5 Department of Basic Medical Science, University of Missouri-Kansas City, Kansas City, USA.
authors: Xiang-Ping
authors: XP
authors: Chu
authors: 4 Department of Neurobiology, Morehouse School of Medicine, Atlanta, USA.
authors: Zhi-Gang
authors: ZG
authors: Xiong
authors: 1 Department of Physiology and Cell Biology, University of South Alabama, Mobile, USA.
authors: Xiang-Ming
authors: XM
authors: Zha
mesh_terms: D062565:Acid Sensing Ion Channels / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000138:Acidosis; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection
chemical_list: C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels
keywords: Acidosis; acid-sensing ion channel; ischemia; neuronal injury; trafficking