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However, controversies exist as to the true contribution of CFTR to the pH balance in airways and intestine. We therefore compared ion transport properties in newborn wild-type (CFTR+\/+) and CFTR-knockout (CFTR\u2212\/\u2212 piglets). Tracheas of CFTR\u2212\/\u2212 piglets demonstrated typical cartilage malformations and muscle cell bundles. CFTR\u2212\/\u2212 airway epithelial cells showed enhanced lipid peroxidation, suggesting inflammation early in life. CFTR was mainly expressed in airway submucosal glands and was absent in lungs of CFTR\u2212\/\u2212 piglets, while expression of TMEM16A was uncompromised. mRNA levels for TMEM16A, TMEM16F, and \u03b1\u03b2\u03b3ENaC were unchanged in CFTR\u2212\/\u2212 airways, while mRNA for SLC26A9 appeared reduced. CFTR was undetectable in epithelial cells of CFTR\u2212\/\u2212 airways and intestine. Small intestinal epithelium of CFTR\u2212\/\u2212 piglets showed mucus accumulation. Secretion of both electrolytes and mucus was activated by stimulation with prostaglandin E2 and ATP in the intestine of CFTR+\/+, but not of CFTR\u2212\/\u2212 animals. pH was measured inside small bronchi using a pH microelectrode and revealed no difference between CFTR+\/+ and CFTR\u2212\/\u2212 piglets. Intracellular pH in porcine airway epithelial cells revealed only a small contribution of CFTR to bicarbonate secretion, which was absent in cells from CFTR\u2212\/\u2212 piglets. In contrast to earlier reports, our data suggest a minor impact of CFTR on ASL pH. In contrast, enhanced amiloride-sensitive Na<jats:sup>+<\/jats:sup> absorption may contribute to lung pathology in CFTR\u2212\/\u2212 piglets, along with a compromised CFTR- and TMEM16A-dependent Cl<jats:sup>\u2212<\/jats:sup> transport.<\/jats:p>","DOI":"10.1007\/s00424-020-02440-y","type":"journal-article","created":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T08:03:49Z","timestamp":1595664229000},"page":"1507-1519","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Transport properties in CFTR\u2212\/\u2212 knockout piglets suggest normal airway surface liquid pH and enhanced amiloride-sensitive Na+ absorption"],"prefix":"10.1007","volume":"472","author":[{"given":"Roberta","family":"Benedetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Centeio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiraporn","family":"Ousingsawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Janda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6222-4593","authenticated-orcid":false,"given":"Karl","family":"Kunzelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,25]]},"reference":[{"key":"2440_CR1","first-page":"L329","volume":"283","author":"ST Ballard","year":"2002","unstructured":"Ballard ST, Trout L, Mehta A, Inglis SK (2002) Liquid secretion inhibitors reduce mucociliary transport in glandular airways. 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