{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:17:37Z","timestamp":1793121457766,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002839","name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002839","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pflugers Arch - Eur J Physiol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The concept of solvent drag, i.e., water and solutes sharing the same pore and their transport being frictionally coupled, was first proposed in the early 1950s. During the following decades, it was applied to transport processes across cell membranes as well as transport along the paracellular pathway. Water-driven solute transport was proposed as the major mechanism for electrolyte and nutrient absorption in the small intestine and for Cl<jats:sup>\u2212<\/jats:sup> and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2009reabsorption in the renal proximal tubule. With the discovery of aquaporins as transcellular route for water transport and the claudin protein family as the major determinant of paracellular transport properties, new mechanistic insights in transepithelial water and solute transport are emerging and call for a reassessment of the solvent drag concept. Current knowledge does not provide a molecular basis for relevant solvent drag-driven, paracellular nutrient, and inorganic anion (re-)absorption. For inorganic cation transport, in contrast, solvent drag along claudin-2-formed paracellular channels appears feasible.<\/jats:p>","DOI":"10.1007\/s00424-022-02773-w","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T16:58:23Z","timestamp":1669309103000},"page":"277-281","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Is there a molecular basis for solvent drag in the renal proximal tubule?"],"prefix":"10.1007","volume":"475","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-7164","authenticated-orcid":false,"given":"Dorothee","family":"G\u00fcnzel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"2773_CR1","doi-asserted-by":"publisher","unstructured":"Amasheh S, Meiri N, Gitter AH, Sch\u00f6neberg T, Mankertz J, Schulzke JD, Fromm M (2002) Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 115:4969\u20134976. https:\/\/doi.org\/10.1242\/jcs.00165","DOI":"10.1242\/jcs.00165"},{"key":"2773_CR2","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/j.1748-1716.1957.tb01425.x","volume":"39","author":"B Andersen","year":"1957","unstructured":"Andersen B, Ussing HH (1957) Solvent drag on non-electrolytes during osmotic flow through isolated toad skin and its response to antidiuretic hormone. Acta Physiol Scand 39:228\u2013239. https:\/\/doi.org\/10.1111\/j.1748-1716.1957.tb01425.x","journal-title":"Acta Physiol Scand"},{"key":"2773_CR3","doi-asserted-by":"publisher","unstructured":"Ayala-Torres C, Krug SM, Rosenthal R, Fromm M (2021) Angulin-1 (LSR) affects paracellular water transport, however only in tight epithelial cells. Int J Mol Sci 22.https:\/\/doi.org\/10.3390\/ijms22157827","DOI":"10.3390\/ijms22157827"},{"key":"2773_CR4","doi-asserted-by":"publisher","unstructured":"Ayala-Torres C, Krug SM, Schulzke JD, Rosenthal R, Fromm M (2019) Tricellulin effect on paracellular water transport. Int J Mol Sci 20.https:\/\/doi.org\/10.3390\/ijms20225700","DOI":"10.3390\/ijms20225700"},{"key":"2773_CR5","doi-asserted-by":"publisher","unstructured":"Bai G, Yi HB, Li HJ, Xu JJ (2013) Hydration characteristics of Ca2+ and Mg2+: a density functional theory, polarized continuum model and molecular dynamics investigation. Mol Phys 111:553\u2013568. https:\/\/doi.org\/10.1080\/00268976.2012.737035","DOI":"10.1080\/00268976.2012.737035"},{"key":"2773_CR6","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1152\/physrev.1984.64.3.763","volume":"64","author":"PH Barry","year":"1984","unstructured":"Barry PH, Diamond JM (1984) Effects of unstirred layers on membrane phenomena. Physiol Rev 64:763\u2013872. https:\/\/doi.org\/10.1152\/physrev.1984.64.3.763","journal-title":"Physiol Rev"},{"key":"2773_CR7","doi-asserted-by":"publisher","first-page":"F279","DOI":"10.1152\/ajprenal.1983.245.3.F279","volume":"245","author":"CA Berry","year":"1983","unstructured":"Berry CA (1983) Water permeability and pathways in the proximal tubule. Am J Physiol 245:F279-294. https:\/\/doi.org\/10.1152\/ajprenal.1983.245.3.F279","journal-title":"Am J Physiol"},{"key":"2773_CR8","doi-asserted-by":"publisher","unstructured":"Breiderhoff T, Himmerkus N, Meoli L, Fromm A, Sewerin S, Kriuchkova N, Nagel O, Ladilov Y, Krug SM, Quintanova C, Stumpp M, Garbe-Sch\u00f6nberg D, Westernstroer U, Merkel C, Brinkhus MA, Altm\u00fcller J, Schweiger MR, M\u00fcller D, Mutig K, Morawski M, Halbritter J, Milatz S, Bleich M, G\u00fcnzel D (2022) Claudin-10a deficiency shifts proximal tubular Cl- permeability to cation selectivity via claudin-2 redistribution. J Am Soc Nephrol 33:699\u2013717. https:\/\/doi.org\/10.1681\/ASN.2021030286","DOI":"10.1681\/ASN.2021030286"},{"key":"2773_CR9","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/s0006-3495(62)86959-8","volume":"2","author":"G Eisenman","year":"1962","unstructured":"Eisenman G (1962) Cation selective glass electrodes and their mode of operation. Biophys J 2:259\u2013323. https:\/\/doi.org\/10.1016\/s0006-3495(62)86959-8","journal-title":"Biophys J"},{"key":"2773_CR10","doi-asserted-by":"publisher","unstructured":"Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539\u20131550. https:\/\/doi.org\/10.1083\/jcb.141.7.1539","DOI":"10.1083\/jcb.141.7.1539"},{"key":"2773_CR11","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1242\/jcs.040113","volume":"122","author":"D G\u00fcnzel","year":"2009","unstructured":"G\u00fcnzel D, Stuiver M, Kausalya PJ, Haisch L, Krug SM, Rosenthal R, Meij IC, Hunziker W, Fromm M, M\u00fcller D (2009) Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function. J Cell Sci 122:1507\u20131517. https:\/\/doi.org\/10.1242\/jcs.040113","journal-title":"J Cell Sci"},{"key":"2773_CR12","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14794","author":"C Hempel","year":"2022","unstructured":"Hempel C, Rosenthal R, Fromm A, Krug SM, Fromm M, G\u00fcnzel D, Piontek J (2022) Tight junction channels claudin-10b and claudin-15: functional mapping of pore-lining residues. Ann N Y Acad Sci. https:\/\/doi.org\/10.1111\/nyas.14794","journal-title":"Ann N Y Acad Sci"},{"key":"2773_CR13","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1126\/science.1260555","volume":"346","author":"G Hummer","year":"2014","unstructured":"Hummer G (2014) Biochemistry. Potassium ions line up. Science 346:303. https:\/\/doi.org\/10.1126\/science.1260555","journal-title":"Science"},{"key":"2773_CR14","doi-asserted-by":"publisher","unstructured":"Inai T, Kobayashi J, Shibata Y (1999) Claudin-1 contributes to the epithelial barrier function in MDCK cells. Eur J Cell Biol 78:849\u2013855. https:\/\/doi.org\/10.1016\/S0171-9335(99)80086-7","DOI":"10.1016\/S0171-9335(99)80086-7"},{"key":"2773_CR15","doi-asserted-by":"publisher","unstructured":"Koefoed-Johnsen V, Ussing HH (1953) The contributions of diffusion and flow to the passage of D2O through living membranes; effect of neurohypophyseal hormone on isolated anuran skin. Acta Physiol Scand 28:60\u201376. https:\/\/doi.org\/10.1111\/j.1748-1716.1953.tb00959.x","DOI":"10.1111\/j.1748-1716.1953.tb00959.x"},{"key":"2773_CR16","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/mi.2017.52","volume":"11","author":"SM Krug","year":"2018","unstructured":"Krug SM, Bojarski C, Fromm A, Lee IM, Dames P, Richter JF, Turner JR, Fromm M, Schulzke JD (2018) Tricellulin is regulated via interleukin-13-receptor alpha2, affects macromolecule uptake, and is decreased in ulcerative colitis. Mucosal Immunol 11:345\u2013356. https:\/\/doi.org\/10.1038\/mi.2017.52","journal-title":"Mucosal Immunol"},{"key":"2773_CR17","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/S0301-0104(00)00106-3","volume":"258","author":"GH Peslherbe","year":"2000","unstructured":"Peslherbe GH, Ladanyi BM, Hynes JT (2000) Structure of NaI ion pairs in water clusters. Chem Phys 258:201\u2013224. https:\/\/doi.org\/10.1016\/S0301-0104(00)00106-3","journal-title":"Chem Phys"},{"key":"2773_CR18","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1016\/S0006-3495(00)76786-5","volume":"78","author":"P Pohl","year":"2000","unstructured":"Pohl P, Saparov SM (2000) Solvent drag across gramicidin channels demonstrated by microelectrodes. Biophys J 78:2426\u20132434. https:\/\/doi.org\/10.1016\/S0006-3495(00)76786-5","journal-title":"Biophys J"},{"key":"2773_CR19","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/apha.12742","volume":"219","author":"R Rosenthal","year":"2017","unstructured":"Rosenthal R, G\u00fcnzel D, Krug SM, Schulzke JD, Fromm M, Yu AS (2017) Claudin-2-mediated cation and water transport share a common pore. Acta Physiol (Oxf) 219:521\u2013536. https:\/\/doi.org\/10.1111\/apha.12742","journal-title":"Acta Physiol (Oxf)"},{"key":"2773_CR20","doi-asserted-by":"publisher","first-page":"e13334","DOI":"10.1111\/apha.13334","volume":"228","author":"R Rosenthal","year":"2020","unstructured":"Rosenthal R, G\u00fcnzel D, Piontek J, Krug SM, Ayala-Torres C, Hempel C, Theune D, Fromm M (2020) Claudin-15 forms a water channel through the tight junction with distinct function compared to claudin-2. Acta Physiol (Oxf) 228:e13334. https:\/\/doi.org\/10.1111\/apha.13334","journal-title":"Acta Physiol (Oxf)"},{"key":"2773_CR21","doi-asserted-by":"publisher","unstructured":"Rosenthal R, Milatz S, Krug SM, Oelrich B, Schulzke JD, Amasheh S, G\u00fcnzel D, Fromm M (2010) Claudin-2, a component of the tight junction, forms a paracellular water channel. J Cell Sci 123:1913\u20131921. https:\/\/doi.org\/10.1242\/jcs.060665","DOI":"10.1242\/jcs.060665"},{"key":"2773_CR22","doi-asserted-by":"publisher","unstructured":"Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP (1999) Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 285:103\u2013106. https:\/\/doi.org\/10.1126\/science.285.5424.103","DOI":"10.1126\/science.285.5424.103"},{"key":"2773_CR23","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1128\/Mcb.00758-15","volume":"36","author":"H Tanaka","year":"2016","unstructured":"Tanaka H, Yamamoto Y, Kashihara H, Yamazaki Y, Tani K, Fujiyoshi Y, Mineta K, Takeuchi K, Tamura A, Tsukita S (2016) Claudin-21 has a paracellular channel role at tight junctions. Mol Cell Biol 36:954\u2013964. https:\/\/doi.org\/10.1128\/Mcb.00758-15","journal-title":"Mol Cell Biol"},{"key":"2773_CR24","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/9780470122587.ch2","volume":"13","author":"HH Ussing","year":"1952","unstructured":"Ussing HH (1952) Some aspects of the application of tracers in permeability studies. Adv Enzymol Relat Subj Biochem 13:21\u201365. https:\/\/doi.org\/10.1002\/9780470122587.ch2","journal-title":"Adv Enzymol Relat Subj Biochem"},{"key":"2773_CR25","unstructured":"Ussing HH, Andersen B The relation between solvent drag and active transport of ions. In: Li\u00e9becq C (ed) Third International Congress of Biochemistry, Brussels, 1955. Acad. Press, New York, 434\u2013440"},{"key":"2773_CR26","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1098\/rspb.1980.0158","volume":"211","author":"G Whittembury","year":"1980","unstructured":"Whittembury G, de Martinez CV, Linares H, Paz-Aliaga A (1980) Solvent drag of large solutes indicates paracellular water flow in leaky epithelia. Proc R Soc Lond B Biol Sci 211:63\u201381. https:\/\/doi.org\/10.1098\/rspb.1980.0158","journal-title":"Proc R Soc Lond B Biol Sci"},{"key":"2773_CR27","doi-asserted-by":"publisher","unstructured":"Yu AS, Cheng MH, Angelow S, G\u00fcnzel D, Kanzawa SA, Schneeberger EE, Fromm M, Coalson RD (2009) Molecular basis for cation selectivity in claudin-2-based paracellular pores: identification of an electrostatic interaction site. J Gen Physiol 133:111\u2013127. https:\/\/doi.org\/10.1085\/jgp.200810154","DOI":"10.1085\/jgp.200810154"},{"key":"2773_CR28","doi-asserted-by":"publisher","unstructured":"Zhou YF, Morais-Cabral JH, Kaufman A, MacKinnon R (2001) Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 angstrom resolution. Nature 414:43\u201348. https:\/\/doi.org\/10.1038\/35102009","DOI":"10.1038\/35102009"}],"container-title":["Pfl\u00fcgers Archiv - European Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-022-02773-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00424-022-02773-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-022-02773-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T06:07:30Z","timestamp":1674022050000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00424-022-02773-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,23]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["2773"],"URL":"https:\/\/doi.org\/10.1007\/s00424-022-02773-w","relation":{},"ISSN":["0031-6768","1432-2013"],"issn-type":[{"value":"0031-6768","type":"print"},{"value":"1432-2013","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,23]]},"assertion":[{"value":"17 October 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The author declares no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}