{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:00:47Z","timestamp":1793325647809,"version":"4.5.0"},"reference-count":0,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1996,1,1]]},"abstract":"<jats:p> Liddle's disease is an autosomal dominant genetic disorder characterized by severe low renin hypertension (\"pseudoaldosteronism\") that has been genetically linked to a locus on chromosome 16 encoding the beta-subunit of an amiloride-sensitive Na+ channel (ASSC) (15). Peripheral blood lymphocytes (PBL) express ASSC that are functionally indistinguishable from those expressed by Na(+)-reabsorbing renal epithelial cells (3, 5). The amiloride-sensitive Na+ conductance in PBL from affected and unaffected individuals from the original Liddle's pedigree was examined using whole cell patch clamp. Typically, the basal Na+ currents in cells from affected individuals were maximally activated. Basal Na+ currents in cells from unaffected individuals were minimal and could be maximally activated by superfusion with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP). Affected cells could not be further stimulated with CPT-cAMP. Superfusion with a supermaximal concentration of amiloride (2 microM) inhibited both the cAMP-activated Na+ conductance in unaffected cells and the constitutively activated inward conductance in affected cells. Cytosolic addition of a peptide identical to the terminal 10 amino acids of the truncated beta-subunit normalized the cAMP-mediated but not the pertussis toxin-induced regulation of the mutant ASSC. The findings show that lymphocyte ASSC are constitutively activated in affected individuals, that a mutation of the beta-subunit alters ASSC responsiveness to specific regulatory effectors, and that the cellular mechanism responsible for the pathophysiology of Liddle's disease is abnormal regulation of Na+ channel activity. These findings have important diagnostic and therapeutic implications and provide a cellular phenotype for the diagnosis of pseudoaldosteronism. <\/jats:p>","DOI":"10.1152\/ajpcell.1996.270.1.c208","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T19:09:09Z","timestamp":1514142549000},"page":"C208-C213","source":"Crossref","is-referenced-by-count":61,"title":["Liddle's disease: abnormal regulation of amiloride-sensitive Na+ channels by beta-subunit mutation"],"prefix":"10.1152","volume":"270","author":[{"given":"J. K.","family":"Bubien","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. I.","family":"Ismailov","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. K.","family":"Berdiev","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Cornwell","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. P.","family":"Lifton","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Achard","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Benos","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. G.","family":"Warnock","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1996.270.1.C208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:37:18Z","timestamp":1718653038000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1996.270.1.C208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1996,1,1]]}},"alternative-id":["10.1152\/ajpcell.1996.270.1.C208"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1996.270.1.c208","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,1,1]]}}}