{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:54:57Z","timestamp":1787730897897,"version":"build-2784847793"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H01751"],"award-info":[{"award-number":["16H01751"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Magnesium plays important roles in the nervous system. An increase in the Mg2+ concentration in cerebrospinal fluid enhances neural functions, while Mg2+ deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg2+ due to the release of Mg2+ from mitochondria, followed by a decrease to below steady-state levels. Since Mg2+ deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg2+ decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg2+ extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg2+ release from mitochondria and Mg2+ extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg2+ concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg2+ regulation in neuronal survival under excitotoxicity.<\/jats:p>","DOI":"10.3390\/nu12092768","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T22:58:01Z","timestamp":1599778681000},"page":"2768","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of Mg2+ Extrusion Attenuates Glutamate Excitotoxicity in Cultured Rat Hippocampal Neurons"],"prefix":"10.3390","volume":"12","author":[{"given":"Yutaka","family":"Shindo","sequence":"first","affiliation":[{"name":"Department of Bioscience and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4678-1899","authenticated-orcid":false,"given":"Ryu","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Yamaguchi 756-0884, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4614-7473","authenticated-orcid":false,"given":"Kohji","family":"Hotta","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan"},{"name":"Waseda Research Institute for Science and Engineering, Waseda University, Shinjuku, Tokyo 162-8480, Japan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yamanaka, R., Shindo, Y., and Oka, K. 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