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      Human ASIC1a mediates stronger acid-induced responses as compared with mouse ASIC1a

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          Abstract

          Acid-sensing ion channels (ASICs) are the major proton receptor in the brain and a key mediator of acidosis-induced neuronal injuries in disease. Most of published data on ASIC function came from studies performed in mice, and relatively little is known about potential differences between human and mouse ASICs (hASIC and mASIC, respectively). This information is critical for us to better interpret the functional importance of ASICs in human disease. Here, we examined the expression of ASICs in acutely resected human cortical tissue. Compared with mouse cortex, human cortical tissue showed a similar ratio of ASIC1a:ASIC2a expression, had reduced ASIC2b level, and exhibited a higher membrane:total ratio of ASIC1a. We further investigated the mechanism for higher surface trafficking of hASIC1a in heterologous cells. A single amino acid at position 285 was critical for increased N-glycosylation and surface expression of hASIC1a. Consistent with the changes in trafficking and current, cells expressing hASIC1a or mASIC1a S285P mutant had a higher acid-activated calcium increase and exhibited worsened acidotoxicity. These data suggest that ASICs are likely to have a larger impact on acidosis-induced neuronal injuries in humans than mice, and this effect is, at least in part, a result of more efficient trafficking of hASIC1a.—Xu, Y., Jiang, Y.-Q., Li, C., He, M., Rusyniak, W. G., Annamdevula, N., Ochoa, J., Leavesley, S. J., Xu, J., Rich, T. C., Lin, M. T., Zha, X.-M. Human ASIC1a mediates stronger acid-induced responses as compared with mouse ASIC1a.

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          Author and article information

          Journal
          FASEB J
          FASEB J
          fasebj
          fasebj
          The FASEB Journal
          Federation of American Societies for Experimental Biology (Bethesda, MD, USA )
          0892-6638
          1530-6860
          July 2018
          15 February 2018
          1 July 2019
          : 32
          : 7
          : 3832-3843
          Affiliations
          [* ]Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, Alabama, USA;
          []Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China;
          []The Third Hospital of Hebei Medical University, ShiJiaZhuang, China;
          [§ ]Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China;
          []Department of Neurosurgery, College of Medicine, University of South Alabama, Mobile, Alabama, USA;
          []Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, Alabama, USA;
          [# ]Department of Neurology, College of Medicine, University of South Alabama, Mobile, Alabama, USA;
          [** ]Chemical and Biomolecular Engineering, College of Engineering, University of South Alabama, Mobile, Alabama, USA
          Author notes
          [1]

          These authors contributed equally to this work.

          [2 ]Correspondence: Department of Neuropharmacology and Drug Discovery, Southern Medical University, Guangzhou, China. E-mail: jpx@ 123456sum.edu.cn
          [3 ]Correspondence: Department of Physiology and Cell Biology, University of South Alabama College of Medicine, 5851 USA Dr. N., MSB3074, Mobile, AL 36688, USA. E-mail: zha@ 123456southalabama.edu
          Article
          PMC5998965 PMC5998965 5998965 FJ_201701367R
          10.1096/fj.201701367R
          5998965
          29447005
          857c2049-6880-4016-ad08-319ce6117c3d
          © FASEB
          History
          : 20 November 2017
          : 05 February 2018
          Page count
          Figures: 7, Tables: 0, Equations: 1, References: 50, Pages: 12
          Categories
          Research
          Custom metadata
          v1

          calcium,neuronal injury,trafficking,acidosis
          calcium, neuronal injury, trafficking, acidosis

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