{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:07:32Z","timestamp":1791551252196,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19AIREA34470007"],"award-info":[{"award-number":["19AIREA34470007"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["R01NS066027"],"award-info":[{"award-number":["R01NS066027"]}]},{"name":"Research Centers in Minority Institutions","award":["U54MD007602"],"award-info":[{"award-number":["U54MD007602"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation Grant","doi-asserted-by":"crossref","award":["2401892"],"award-info":[{"award-number":["2401892"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acid-sensing ion channels (ASICs), activated under acidic conditions, play a critical role in ischemic brain injury, but the detailed mechanisms and signaling pathways remain unclear. Our previous studies have shown that activation of ASIC1a channels contributes to acidosis-induced neuronal injury, partially mediated by increased calcium influx. In this study, we provide evidence that activation of ASIC2a-containing channels induces zinc influx. In cultured mouse cortical neurons, ASIC currents that were insensitive to PcTx1 inhibition were potentiated by extracellular zinc. In Chinese Hamster Ovary cells transfected with different ASIC subunits, large inward currents were recorded upon a pH drop from 7.4 to 5.0 in cells expressing homomeric ASIC1a, ASIC2a, or heteromeric ASIC1a\/2a channels when normal Na+-rich extracellular fluid (ECF) was used. However, when ECF was modified to one containing zinc as the primary cation, the same pH drop induced an inward current only in cells expressing homomeric ASIC2a or heteromeric ASIC1a\/2a, but not homomeric ASIC1a. Fluorescence imaging revealed rapid zinc influx in cells expressing ASIC2a but not ASIC1a when zinc was applied with the acidic ECF. Additionally, at pH values where ASIC2a-containing channels were activated, acid-mediated neurotoxicity was exacerbated by zinc. Thus, ASIC2a-containing channels may represent a novel pathway for zinc entry and activation of these channels might contribute to zinc-mediated neurotoxicity.<\/jats:p>","DOI":"10.3390\/cells15020186","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:36:33Z","timestamp":1768898193000},"page":"186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Zinc Permeation Through Acid-Sensing Ion Channels"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6781-0468","authenticated-orcid":false,"given":"Xiang-Ping","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5481-569X","authenticated-orcid":false,"given":"Koichi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA"},{"name":"Department of Anatomy and Cell Biology, Nara Medical University, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2824-4168","authenticated-orcid":false,"given":"Zhi-Gang","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1056\/NEJMoa1804492","article-title":"Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016","volume":"379","author":"Feigin","year":"2018","journal-title":"N. 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