title: Regulated acid-base transport in the collecting duct.
abstract: The renal collecting system serves the fine-tuning of renal acid-base secretion. Acid-secretory type-A intercalated cells secrete protons via a luminally expressed V-type H(+)-ATPase and generate new bicarbonate released by basolateral chloride/bicarbonate exchangers including the AE1 anion exchanger. Efficient proton secretion depends both on the presence of titratable acids (mainly phosphate) and the concomitant secretion of ammonia being titrated to ammonium. Collecting duct ammonium excretion requires the Rhesus protein RhCG as indicated by recent KO studies. Urinary acid secretion by type-A intercalated cells is strongly regulated by various factors among them acid-base status, angiotensin II and aldosterone, and the Calcium-sensing receptor. Moreover, urinary acidification by H(+)-ATPases is modulated indirectly by the activity of the epithelial sodium channel ENaC. Bicarbonate secretion is achieved by non-type-A intercalated cells characterized by the luminal expression of the chloride/bicarbonate exchanger pendrin. Pendrin activity is driven by H(+)-ATPases and may serve both bicarbonate excretion and chloride reabsorption. The activity and expression of pendrin is regulated by different factors including acid-base status, chloride delivery, and angiotensin II and may play a role in NaCl retention and blood pressure regulation. Finally, the relative abundance of type-A and non-type-A intercalated cells may be tightly regulated. Dysregulation of intercalated cell function or abundance causes various syndromes of distal renal tubular acidosis underlining the importance of these processes for acid-base homeostasis.
authors.affiliation: Zurich Center for Human Integrative Physiology, University of Zurich, Switzerland. Wagnerca@access.uzh.ch
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Soline
authors.initials: S
authors.lastname: Bourgeois
authors.forename: Nilufar
authors.initials: N
authors.lastname: Mohebbi
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology*; D000141:Acidosis, Renal Tubular / Q000503:physiopathology; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D053503:Epithelial Sodium Channels; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000502:physiology* / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000503:physiopathology; D006180:Proton-Translocating ATPases / Q000378:metabolism; D000076988:Sulfate Transporters; D027981:Symporters / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D001639:Bicarbonates; D027682:Cation Transport Proteins; D053503:Epithelial Sodium Channels; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D006180:Proton-Translocating ATPases; D000076988:Sulfate Transporters; D027981:Symporters; D025262:Vacuolar Proton-Translocating ATPases; C413213:RHCG protein, human; C119651:SLC12A7 protein, human; D000096922:K Cl- Cotransporters; C085609:SLC26A4 protein, human