{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:43:37Z","timestamp":1772995417708,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["STO 1260\/1\u20101"],"award-info":[{"award-number":["STO 1260\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013865","name":"Stiftung Charit\u00e9","doi-asserted-by":"publisher","award":["BIH_PRO_406"],"award-info":[{"award-number":["BIH_PRO_406"]}],"id":[{"id":"10.13039\/501100013865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The zona glomerulosa (ZG) of the adrenal cortex regulates blood pressure and electrolyte homeostasis through aldosterone production. In ZG cells, potassium and angiotensin II (Ang II) trigger calcium oscillations that drive aldosterone synthesis. Changes in serum osmolality also modulate aldosterone production in a chloride\u2010dependent fashion, but the involved proteins remain unclear. Because the chloride channel ClC\u20102 is activated by hypoosmolality, we investigated its role in ZG osmoregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used\n                      <jats:italic>Clcn2<\/jats:italic>\n                      knockout (KO) and wild\u2010type (WT) mice. Explanted adrenal glands were incubated with iso\u2010 and hypotonic solutions for measurements of aldosterone. Acute adrenal slices were studied using calcium and chloride sensitive fluorescent dyes. We also investigated ClC\u20102's systemic importance by inducing a hyponatremic hypoosmolality in mice using desmopressin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Under hypoosmolar conditions, WT adrenals upregulated aldosterone production in\u00a0vitro, an effect that was absent in the KO. WT cells responded to hypoosmolality with increased intracellular calcium levels. This response was abrogated in KO cells. Intracellular chloride levels were higher in ZG cells from KO adrenal slices. This suggests that ClC\u20102 provides a hypoosmolality\u2010dependent chloride efflux pathway that is missing in the KO. Systemic hypoosmolality in mice induced by desmopressin did not differentially affect blood aldosterone levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ClC\u20102 plays a role in the ZG's response to reduced extracellular osmolality through chloride outflow, which likely causes depolarization, voltage\u2010dependent calcium influx, and aldosterone production. These data advance our understanding of regulators of aldosterone production.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70168","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T04:50:35Z","timestamp":1769662235000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ClC<\/scp>\n                    \u20102 Contributes to Hypotonicity\u2010Induced Adrenal Aldosterone Secretion"],"prefix":"10.1111","volume":"242","author":[{"given":"Marina","family":"Volkert","sequence":"first","affiliation":[{"name":"Center of Genomic Medicine Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoang An","family":"Dinh","sequence":"additional","affiliation":[{"name":"Center of Genomic Medicine Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Institute of Translational Physiology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute I.","family":"Scholl","sequence":"additional","affiliation":[{"name":"Center of Genomic Medicine Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Department of Nephrology and Medical Intensive Care Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"St\u00f6lting","sequence":"additional","affiliation":[{"name":"Center of Genomic Medicine Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.07.034"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-024-02908-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61996"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.21798"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2003"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198785"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2716"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2695"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.06315","article-title":"Recurrent Gain of Function Mutation in Calcium Channel CACNA1H Causes Early\u2010Onset Hypertension With Primary Aldosteronism","volume":"4","author":"Scholl U. 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