{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:14:51Z","timestamp":1760188491559},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,6,9]],"date-time":"2005-06-09T00:00:00Z","timestamp":1118275200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> WNK [With No K (lysine)] kinases are essential for regulation of blood pressure and potassium homeostasis. WNK4 expression was recently found not only in the distal nephron but also in chloride\u2010transporting epithelia. To establish a physiological role for this distribution we studied patients with familial hyperkalaemia and hypertension (FHH), [pseudohypoaldosteronism type II (PHAII)], which is caused by mutations in WNK4.<\/jats:p><jats:p><jats:bold>Design\u2002<\/jats:bold> Measurement of nasal potential difference (NPD) and sweat electrolytes were performed in controls, in six subjects with FHH and ten subjects with cystic fibrosis (CF).<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Basal NPD was higher in FHH compared with controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a020): 22\u00b78\u00a0\u00b1\u00a05\u00b77 vs. 16\u00b72\u00a0\u00b1\u00a05\u00b73\u00a0mV, respectively (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7014). Maximal response to amiloride was also higher in FHH compared with controls: 14\u00b78\u00a0\u00b1\u00a03\u00b75 vs. 10\u00b70\u00a0\u00b1\u00a04\u00b78\u00a0mV, respectively (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b703). In CF these values were 42\u00b79\u00a0\u00b1\u00a09\u00b73 and 29\u00b79\u00a0\u00b1\u00a07\u00b74\u00a0mV, respectively. The kinetics of the amiloride effect were faster in FHH, and as first reported here also in CF, compared with controls. At 30\u00a0s, amiloride\u2010inhibitable residual PD in FHH was 50\u00a0\u00b1\u00a030 vs. 81\u00a0\u00b1\u00a09% in controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b70003) and 56\u00a0\u00b1\u00a07% in CF. The response to chloride\u2010free and isoproterenol solutions, which determines chloride transport activity, was similar in FHH compared with controls [16\u00b70\u00a0\u00b1\u00a08\u00b76 vs. 10\u00b74\u00a0\u00b1\u00a05\u00b79\u00a0mV (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b708)]. Sweat conductivity in FHH was 49\u00b77\u00a0\u00b1\u00a07\u00b73 vs. 38\u00b72\u00a0\u00b1\u00a08\u00b71\u00a0mmol (NaCl eq) L<jats:sup>\u22121<\/jats:sup> in 16 controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7007) and 94\u00b70\u00a0\u00b1\u00a019\u00b73 in CF.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Mutant WNK4 increases Na<jats:sup>+<\/jats:sup> transport in airways, and therefore it is regulated by wild\u2010type WNK4. This may be caused by a regulation of ENaC or a K<jats:sup>+<\/jats:sup> channel.<\/jats:p>","DOI":"10.1111\/j.1365-2362.2005.01504.x","type":"journal-article","created":{"date-parts":[[2005,6,9]],"date-time":"2005-06-09T09:59:44Z","timestamp":1118311184000},"page":"410-415","source":"Crossref","is-referenced-by-count":19,"title":["WNK4 regulates Na<sup>+<\/sup> transport in 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