{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T02:00:59Z","timestamp":1782871259977,"version":"3.54.5"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"11","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":706,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T00:00:00Z","timestamp":1525651200000},"content-version":"vor","delay-in-days":206,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-1515434"],"award-info":[{"award-number":["MCB-1515434"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15-GM061583"],"award-info":[{"award-number":["R15-GM061583"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17PRE32860001"],"award-info":[{"award-number":["17PRE32860001"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,11,6]]},"abstract":"<jats:p>Primary aldosteronism, a condition in which too much aldosterone is produced and that leads to hypertension, is often initiated by an aldosterone-producing adenoma within the zona glomerulosa of the adrenal cortex. Somatic mutations of ATP1A1, encoding the Na\/K pump \u03b11 subunit, have been found in these adenomas. It has been proposed that a passive inward current transported by several of these mutant pumps is a \"gain-of-function\" activity that produces membrane depolarization and concomitant increases in aldosterone production. Here, we investigate whether the inward current through mutant Na\/K pumps is large enough to induce depolarization of the cells that harbor them. We first investigate inward currents induced by these mutations in Xenopus Na\/K pumps expressed in Xenopus oocytes and find that these inward currents are similar in amplitude to wild-type outward Na\/K pump currents. Subsequently, we perform a detailed functional evaluation of the human Na\/K pump mutants L104R, delF100-L104, V332G, and EETA963S expressed in Xenopus oocytes. By combining two-electrode voltage clamp with [3H]ouabain binding, we measure the turnover rate of these inward currents and compare it to the turnover rate for outward current through wild-type pumps. We find that the turnover rate of the inward current through two of these mutants (EETA963S and L104R) is too small to induce significant cell depolarization. Electrophysiological characterization of another hyperaldosteronism-inducing mutation, G99R, reveals the absence of inward currents under many different conditions, including in the presence of the regulator FXYD1 as well as with mammalian ionic concentrations and body temperatures. Instead, we observe robust outward currents, but with significantly reduced affinities for intracellular Na+ and extracellular K+. Collectively, our results point to loss-of-function as the common mechanism for the hyperaldosteronism induced by these Na\/K pump mutants.<\/jats:p>","DOI":"10.1085\/jgp.201711827","type":"journal-article","created":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T14:10:20Z","timestamp":1507903820000},"page":"1009-1028","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["On the effect of hyperaldosteronism-inducing mutations in Na\/K pumps"],"prefix":"10.1085","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-3813","authenticated-orcid":true,"given":"Dylan J.","family":"Meyer","sequence":"first","affiliation":[{"name":"Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 1"},{"name":"School of Biological Sciences, Illinois State University, Normal, IL 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Gatto","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Illinois State University, Normal, IL 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6893-9765","authenticated-orcid":true,"given":"Pablo","family":"Artigas","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,10,13]]},"reference":[{"key":"2023072623572203900_bib1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1530\/ERC-15-0321","article-title":"Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas","volume":"22","author":"\u00c5kerstr\u00f6m","year":"2015","journal-title":"Endocr. Relat. Cancer."},{"key":"2023072623572203900_bib2","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1085\/jgp.200308964","article-title":"Large diameter of palytoxin-induced Na\/K pump channels and modulation of palytoxin interaction by Na\/K pump ligands","volume":"123","author":"Artigas","year":"2004","journal-title":"J. Gen. Physiol."},{"key":"2023072623572203900_bib3","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1097\/MED.0000000000000255","article-title":"Novel genetic determinants of adrenal aldosterone regulation","volume":"23","author":"Azizan","year":"2016","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"2023072623572203900_bib4","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/ng.2716","article-title":"Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension","volume":"45","author":"Azizan","year":"2013","journal-title":"Nat. Genet."},{"key":"2023072623572203900_bib5","doi-asserted-by":"publisher","first-page":"5851","DOI":"10.1113\/JP271896","article-title":"Role of voltage-gated calcium channels in the regulation of aldosterone production from zona glomerulosa cells of the adrenal cortex","volume":"594","author":"Barrett","year":"2016","journal-title":"J. Physiol."},{"key":"2023072623572203900_bib6","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/ng.2550","article-title":"Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension","volume":"45","author":"Beuschlein","year":"2013","journal-title":"Nat. Genet."},{"key":"2023072623572203900_bib7","first-page":"F633","article-title":"Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function","volume":"275","author":"Blanco","year":"1998","journal-title":"Am. J. Physiol."},{"key":"2023072623572203900_bib8","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1002\/j.1460-2075.1992.tb05218.x","article-title":"Mutation of a cysteine in the first transmembrane segment of Na,K-ATPase alpha subunit confers ouabain resistance","volume":"11","author":"Canessa","year":"1992","journal-title":"EMBO J."},{"key":"2023072623572203900_bib9","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1126\/science.1198785","article-title":"K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension","volume":"331","author":"Choi","year":"2011","journal-title":"Science."},{"key":"2023072623572203900_bib10","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1074\/jbc.275.3.1976","article-title":"Transport and pharmacological properties of nine different human Na, K-ATPase isozymes","volume":"275","author":"Crambert","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2023072623572203900_bib11","doi-asserted-by":"publisher","first-page":"L1","DOI":"10.1530\/ERC-13-0466","article-title":"Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas","volume":"21","author":"Dutta","year":"2014","journal-title":"Endocr. Relat. Cancer."},{"key":"2023072623572203900_bib12","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1161\/HYPERTENSIONAHA.114.03419","article-title":"Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma","volume":"64","author":"Fernandes-Rosa","year":"2014","journal-title":"Hypertension."},{"key":"2023072623572203900_bib13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.aanat.2009.09.003","article-title":"Differential cellular expression of FXYD1 (phospholemman) and FXYD2 (gamma subunit of Na, K-ATPase) in normal human tissues: a study using high density human tissue microarrays","volume":"192","author":"Floyd","year":"2010","journal-title":"Ann. Anat."},{"key":"2023072623572203900_bib14","doi-asserted-by":"crossref","first-page":"11104","DOI":"10.1016\/S0021-9258(18)60932-9","article-title":"Rapid release of 42K and 86Rb from an occluded state of the Na,K-pump in the presence of ATP or ADP","volume":"262","author":"Forbush","year":"1987","journal-title":"J. Biol. Chem."},{"key":"2023072623572203900_bib15","doi-asserted-by":"crossref","first-page":"11116","DOI":"10.1016\/S0021-9258(18)60933-0","article-title":"Rapid release of 42K or 86Rb from two distinct transport sites on the Na,K-pump in the presence of Pi or vanadate","volume":"262","author":"Forbush","year":"1987","journal-title":"J. Biol. Chem."},{"key":"2023072623572203900_bib16","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.ab.2012.03.028","article-title":"Soymilk: an effective and inexpensive blocking agent for immunoblotting","volume":"426","author":"Galva","year":"2012","journal-title":"Anal. Biochem."},{"key":"2023072623572203900_bib17","doi-asserted-by":"crossref","first-page":"C982","DOI":"10.1152\/ajpcell.2001.281.3.C982","article-title":"Heterologous expression of Na(+)-K(+)-ATPase in insect cells: intracellular distribution of pump subunits","volume":"281","author":"Gatto","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2023072623572203900_bib18","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1097\/MNH.0b013e3283036cbf","article-title":"Functional roles of Na,K-ATPase subunits","volume":"17","author":"Geering","year":"2008","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"2023072623572203900_bib19","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.mce.2014.12.004","article-title":"Somatic mutations of the ATP1A1 gene and aldosterone-producing adenomas","volume":"408","author":"Gomez-Sanchez","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072623572203900_bib20","first-page":"1637","article-title":"Angiotensin-II inhibits Na+\/K+ pump in rat adrenal glomerulosa cells: possible contribution to stimulation of aldosterone production","volume":"130","author":"Hajn\u00f3czky","year":"1992","journal-title":"Endocrinology."},{"key":"2023072623572203900_bib21","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1530\/EJE-11-1013","article-title":"Screening for primary aldosteronism in hypertensive subjects: results from two German epidemiological studies","volume":"167","author":"Hannemann","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"2023072623572203900_bib22","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1073\/pnas.1617951114","article-title":"Arginine substitution of a cysteine in transmembrane helix M8 converts Na+,K+-ATPase to an electroneutral pump similar to H+,K+-ATPase","volume":"114","author":"Holm","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072623572203900_bib23","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1529\/biophysj.105.072942","article-title":"Charge translocation by the Na+\/K+ pump under Na+\/Na+ exchange conditions: intracellular Na+ dependence","volume":"90","author":"Holmgren","year":"2006","journal-title":"Biophys. J."},{"key":"2023072623572203900_bib24","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/35002599","article-title":"Three distinct and sequential steps in the release of sodium ions by the Na+\/K+-ATPase","volume":"403","author":"Holmgren","year":"2000","journal-title":"Nature."},{"key":"2023072623572203900_bib25","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1172\/JCI61996","article-title":"Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators","volume":"122","author":"Hu","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2023072623572203900_bib26","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/nature12578","article-title":"Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state","volume":"502","author":"Kanai","year":"2013","journal-title":"Nature."},{"key":"2023072623572203900_bib27","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1146\/annurev.biochem.71.102201.141218","article-title":"Biochemistry of Na,K-ATPase","volume":"71","author":"Kaplan","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"2023072623572203900_bib28","doi-asserted-by":"publisher","first-page":"51213","DOI":"10.1074\/jbc.M306384200","article-title":"Electrophysiological analysis of the mutated Na,K-ATPase cation binding pocket","volume":"278","author":"Koenderink","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2023072623572203900_bib29","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/0006-291X(89)92822-2","article-title":"Na-Ca exchanger as a calcium influx pathway in adrenal glomerulosa cells","volume":"158","author":"Kojima","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023072623572203900_bib30","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1021\/bi401425g","article-title":"Molecular mechanism of Na(+),K(+)-ATPase malfunction in mutations characteristic of adrenal hypertension","volume":"53","author":"Kopec","year":"2014","journal-title":"Biochemistry."},{"key":"2023072623572203900_bib31","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature."},{"key":"2023072623572203900_bib32","doi-asserted-by":"publisher","first-page":"12706","DOI":"10.1073\/pnas.0505980102","article-title":"A third Na+-binding site in the sodium pump","volume":"102","author":"Li","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072623572203900_bib33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00232-006-0035-0","article-title":"The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current","volume":"213","author":"Li","year":"2006","journal-title":"J. Membr. Biol."},{"key":"2023072623572203900_bib34","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0303-7207(01)00384-7","article-title":"Role of membrane depolarization and T-type Ca2+ channels in angiotensin II and K+ stimulated aldosterone secretion","volume":"175","author":"Lotshaw","year":"2001","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072623572203900_bib35","doi-asserted-by":"crossref","first-page":"10035","DOI":"10.1016\/S0021-9258(18)61070-1","article-title":"Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes","volume":"262","author":"Matsudaira","year":"1987","journal-title":"J. Biol. Chem."},{"key":"2023072623572203900_bib36","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1113\/jphysiol.1973.sp010333","article-title":"Ionic dependence of adrenal steroidogenesis and ACTH-induced changes in the membrane potential of adrenocortical cells","volume":"234","author":"Matthews","year":"1973","journal-title":"J. Physiol."},{"key":"2023072623572203900_bib37","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1085\/jgp.200910301","article-title":"Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+\/K+-ATPase alpha subunit","volume":"135","author":"Meier","year":"2010","journal-title":"J. Gen. Physiol."},{"key":"2023072623572203900_bib38","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1016\/j.bpj.2014.04.053","article-title":"Sodium and proton effects on inward proton transport through Na\/K pumps","volume":"106","author":"Mitchell","year":"2014","journal-title":"Biophys. J."},{"key":"2023072623572203900_bib39","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1210\/jc.2003-031337","article-title":"Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents","volume":"89","author":"Mulatero","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023072623572203900_bib40","first-page":"E158","article-title":"Electrical responses in cat adrenal cortex: possible relation to aldosterone secretion","volume":"237","author":"Natke","year":"1979","journal-title":"Am. J. Physiol."},{"key":"2023072623572203900_bib41","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.mce.2016.10.014","article-title":"Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism","volume":"441","author":"Nishimoto","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072623572203900_bib42","doi-asserted-by":"publisher","first-page":"8400","DOI":"10.1021\/bi00422a016","article-title":"Structure-function relationships in the sodium-potassium-ATPase alpha subunit: site-directed mutagenesis of glutamine-111 to arginine and asparagine-122 to aspartic acid generates a ouabain-resistant enzyme","volume":"27","author":"Price","year":"1988","journal-title":"Biochemistry."},{"key":"2023072623572203900_bib43","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1085\/jgp.200709770","article-title":"Sodium flux ratio in Na\/K pump-channels opened by palytoxin","volume":"130","author":"Rakowski","year":"2007","journal-title":"J. Gen. Physiol."},{"key":"2023072623572203900_bib44","doi-asserted-by":"publisher","first-page":"18718","DOI":"10.1073\/pnas.1004214107","article-title":"Selectivity of externally facing ion-binding sites in the Na\/K pump to alkali metals and organic cations","volume":"107","author":"Ratheal","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072623572203900_bib45","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1016\/j.jacc.2006.07.059","article-title":"A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients","volume":"48","author":"Rossi","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"2023072623572203900_bib46","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1085\/jgp.201711826","article-title":"No fuzzy space for intracellular Na(+) in healthy ventricular myocytes","volume":"149","author":"Sachse","year":"2017","journal-title":"J. Gen. Physiol."},{"key":"2023072623572203900_bib47","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.mce.2003.10.046","article-title":"Glomerulosa cell--a unique sensor of extracellular K+ concentration","volume":"217","author":"Sp\u00e4t","year":"2004","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072623572203900_bib48","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1016\/j.bpj.2015.09.015","article-title":"Importance of the Voltage Dependence of Cardiac Na\/K ATPase Isozymes","volume":"109","author":"Stanley","year":"2015","journal-title":"Biophys. J."},{"key":"2023072623572203900_bib49","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1016\/j.bpj.2016.09.042","article-title":"Intracellular Requirements for Passive Proton Transport through the Na(+),K(+)-ATPase","volume":"111","author":"Stanley","year":"2016","journal-title":"Biophys. J."},{"key":"2023072623572203900_bib50","doi-asserted-by":"publisher","first-page":"4582","DOI":"10.1210\/en.2015-1466","article-title":"Pathogenesis of Adrenal Aldosterone-Producing Adenomas Carrying Mutations of the Na(+)\/K(+)-ATPase","volume":"156","author":"Stindl","year":"2015","journal-title":"Endocrinology."},{"key":"2023072623572203900_bib51","first-page":"E27","article-title":"Ouabain increases aldosterone release from bovine adrenal glomerulosa cells: role of renin-angiotensin system","volume":"270","author":"Tamura","year":"1996","journal-title":"Am. J. Physiol."},{"key":"2023072623572203900_bib52","doi-asserted-by":"publisher","first-page":"31097","DOI":"10.1074\/jbc.M802771200","article-title":"Diverse functional consequences of mutations in the Na+\/K+-ATPase alpha2-subunit causing familial hemiplegic migraine type 2","volume":"283","author":"Tavraz","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2023072623572203900_bib53","doi-asserted-by":"publisher","first-page":"3186","DOI":"10.1074\/jbc.M113.543272","article-title":"Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease","volume":"289","author":"Toustrup-Jensen","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2023072623572203900_bib54","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1210\/endo.133.3.8365363","article-title":"Angiotensin-II induces changes in the cytosolic sodium concentration in bovine adrenal glomerulosa cells: involvement in the activation of aldosterone biosynthesis","volume":"133","author":"van der Bent","year":"1993","journal-title":"Endocrinology."},{"key":"2023072623572203900_bib55","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1085\/jgp.201010407","article-title":"The two C-terminal tyrosines stabilize occluded Na\/K pump conformations containing Na or K ions","volume":"136","author":"Vedovato","year":"2010","journal-title":"J. Gen. Physiol."},{"key":"2023072623572203900_bib56","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1085\/jgp.201311148","article-title":"Route, mechanism, and implications of proton import during Na+\/K+ exchange by native Na+\/K+-ATPase pumps","volume":"143","author":"Vedovato","year":"2014","journal-title":"J. Gen. Physiol."},{"key":"2023072623572203900_bib57","doi-asserted-by":"crossref","first-page":"C590","DOI":"10.1152\/ajpcell.1995.268.3.C590","article-title":"A conformation of Na(+)-K+ pump is permeable to proton","volume":"268","author":"Wang","year":"1995","journal-title":"Am. J. Physiol."},{"key":"2023072623572203900_bib58","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1161\/HYPERTENSIONAHA.113.01733","article-title":"Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas","volume":"63","author":"Williams","year":"2014","journal-title":"Hypertension."},{"key":"2023072623572203900_bib59","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1161\/HYPERTENSIONAHA.115.06186","article-title":"Genotype-Specific Steroid Profiles Associated With Aldosterone-Producing Adenomas","volume":"67","author":"Williams","year":"2016","journal-title":"Hypertension."},{"key":"2023072623572203900_bib60","doi-asserted-by":"publisher","first-page":"11396","DOI":"10.1038\/srep11396","article-title":"Prevalence and clinical correlates of somatic mutation in aldosterone producing adenoma-Taiwanese population","volume":"5","author":"Wu","year":"2015","journal-title":"Sci. Rep."},{"key":"2023072623572203900_bib61","doi-asserted-by":"publisher","first-page":"15507","DOI":"10.1073\/pnas.0903752106","article-title":"Altered Na+ transport after an intracellular alpha-subunit deletion reveals strict external sequential release of Na+ from the Na\/K pump","volume":"106","author":"Yaragatupalli","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072623572203900_bib62","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1016\/S0026-0495(99)90133-6","article-title":"Insights into the mechanism by which inhibition of Na,K-ATPase stimulates aldosterone production","volume":"48","author":"Yingst","year":"1999","journal-title":"Metabolism."},{"key":"2023072623572203900_bib63","doi-asserted-by":"crossref","first-page":"C119","DOI":"10.1152\/ajpcell.2001.280.1.C119","article-title":"Effects of extracellular calcium and potassium on the sodium pump of rat adrenal glomerulosa cells","volume":"280","author":"Yingst","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2023072623572203900_bib64","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1161\/HYPERTENSIONAHA.114.03346","article-title":"Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma","volume":"65","author":"Zheng","year":"2015","journal-title":"Hypertension."}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/149\/11\/1009\/1796387\/jgp_201711827.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/149\/11\/1009\/1796387\/jgp_201711827.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T23:57:56Z","timestamp":1690415876000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/149\/11\/1009\/43543\/On-the-effect-of-hyperaldosteronism-inducing"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,13]]},"references-count":64,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11,6]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.201711827","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,13]]}}}