{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:53:39Z","timestamp":1787504019984,"version":"build-2736575974"},"reference-count":91,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK098141"],"award-info":[{"award-number":["DK098141"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"\n The genetic disease Gitelman syndrome, knockout mice, and pharmacological blockade with thiazide diuretics have revealed that reduced activity of the NaCl cotransporter (NCC) promotes renal Mg\n 2+<\/jats:sup>\n wasting. NCC is expressed along the distal convoluted tubule (DCT), and its activity determines Mg\n 2+<\/jats:sup>\n entry into DCT cells through transient receptor potential channel subfamily M member 6 (TRPM6). Several other genetic forms of hypomagnesemia lower the drive for Mg\n 2+<\/jats:sup>\n entry by inhibiting activity of basolateral Na\n +<\/jats:sup>\n -K\n +<\/jats:sup>\n -ATPase, and reduced NCC activity may do the same. Lower intracellular Mg\n 2+<\/jats:sup>\n may promote further Mg\n 2+<\/jats:sup>\n loss by directly decreasing activity of Na\n +<\/jats:sup>\n -K\n +<\/jats:sup>\n -ATPase. Lower intracellular Mg\n 2+<\/jats:sup>\n may also lower Na\n +<\/jats:sup>\n -K\n +<\/jats:sup>\n -ATPase indirectly by downregulating NCC. Lower NCC activity also induces atrophy of DCT cells, decreasing the available number of TRPM6 channels. Conversely, a mouse model with increased NCC activity was recently shown to display normal Mg\n 2+<\/jats:sup>\n handling. Moreover, recent studies have identified calcineurin and uromodulin (UMOD) as regulators of both NCC and Mg\n 2+<\/jats:sup>\n handling by the DCT. Calcineurin inhibitors paradoxically cause hypomagnesemia in a state of NCC activation, but this may be related to direct effects on TRPM6 gene expression. In Umod\n \u2212\/\u2212<\/jats:sup>\n mice, the cause of hypomagnesemia may be partly due to both decreased NCC expression and lower TRPM6 expression on the cell surface. This mini-review discusses these new findings and the possible role of altered Na\n +<\/jats:sup>\n flux through NCC and ultimately Na\n +<\/jats:sup>\n -K\n +<\/jats:sup>\n -ATPase in Mg\n 2+<\/jats:sup>\n reabsorption by the DCT.\n <\/jats:p>","DOI":"10.1152\/ajprenal.00463.2020","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T06:54:20Z","timestamp":1604300060000},"page":"F1043-F1053","source":"Crossref","is-referenced-by-count":23,"title":["NaCl cotransporter activity and Mg\n 2+<\/sup>\n handling by the distal convoluted tubule"],"prefix":"10.1152","volume":"319","author":[{"given":"Yujiro","family":"Maeoka","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-6653","authenticated-orcid":false,"given":"James 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