{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:24:48Z","timestamp":1784697888196,"version":"3.55.0"},"reference-count":103,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG), Research Unit 2795 \u201cSynapses under Stress\u201d","award":["Ro2327\/13-2"],"award-info":[{"award-number":["Ro2327\/13-2"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG), Research Unit 2795 \u201cSynapses under Stress\u201d","award":["R01NS130916"],"award-info":[{"award-number":["R01NS130916"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Ro2327\/13-2"],"award-info":[{"award-number":["Ro2327\/13-2"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS130916"],"award-info":[{"award-number":["R01NS130916"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ischemic conditions cause an increase in the sodium concentration of astrocytes, driving the breakdown of ionic homeostasis and exacerbating cellular damage. Astrocytes express high levels of the electrogenic sodium-bicarbonate cotransporter1 (NBCe1), which couples intracellular Na+ homeostasis to regulation of pH and operates close to its reversal potential under physiological conditions. Here, we analyzed its mode of operation during transient energy deprivation via imaging astrocytic pH, Na+, and ATP in organotypic slice cultures of the mouse neocortex, complemented with patch-clamp and ion-selective microelectrode recordings and computational modeling. We found that a 2 min period of metabolic failure resulted in a transient acidosis accompanied by a Na+ increase in astrocytes. Inhibition of NBCe1 increased the acidosis while decreasing the Na+ load. Similar results were obtained when comparing ion changes in wild-type and Nbce1-deficient mice. Mathematical modeling replicated these findings and further predicted that NBCe1 activation contributes to the loss of cellular ATP under ischemic conditions, a result confirmed experimentally using FRET-based imaging of ATP. Altogether, our data demonstrate that transient energy failure stimulates the inward operation of NBCe1 in astrocytes. This causes a significant amelioration of ischemia-induced astrocytic acidification, albeit at the expense of increased Na+ influx and a decline in cellular ATP.<\/jats:p>","DOI":"10.3390\/cells12232675","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T10:24:13Z","timestamp":1700562253000},"page":"2675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inward Operation of Sodium-Bicarbonate Cotransporter 1 Promotes Astrocytic Na+ Loading and Loss of ATP in Mouse Neocortex during Brief Chemical Ischemia"],"prefix":"10.3390","volume":"12","author":[{"given":"Katharina","family":"Everaerts","sequence":"first","affiliation":[{"name":"Institute of Neurobiology, Heinrich Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan","family":"Thapaliya","sequence":"additional","affiliation":[{"name":"Department of Physics, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Pape","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Heinrich Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Durry","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Heinrich Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-7004","authenticated-orcid":false,"given":"Sara","family":"Eitelmann","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Heinrich Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-1597","authenticated-orcid":false,"given":"Eleni","family":"Roussa","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of Medicine, Albert-Ludwigs-Universit\u00e4t Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-8742","authenticated-orcid":false,"given":"Ghanim","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Physics, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-3592","authenticated-orcid":false,"given":"Christine","family":"Rose","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Heinrich Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.neuroscience.2004.06.008","article-title":"Potassium buffering in the central nervous system","volume":"129","author":"Kofuji","year":"2004","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3389\/fphys.2016.00141","article-title":"Managing Brain Extracellular K+ during Neuronal Activity: The Physiological Role of the Na+\/K+-ATPase Subunit Isoforms","volume":"7","author":"Larsen","year":"2016","journal-title":"Front. 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