title: Nongastric H+,K+-ATPase: cell biologic and functional properties.
abstract: Several members of the H+,K+-ATPase family of ion pumps participate in renal K transport. This class of P-type ATPases includes the gastric H+,K+-ATPase as well as a number of nongastric H+,K+-ATPase isoforms. Physiological studies suggest that these enzymes operate predominantly at the apical surfaces of tubule epithelial cells. Although much has been learned about the pattern of H+,K+-ATPase isoform expression and its response to stress, the functional and cell biologic attributes of these pumps remain largely unelucidated. We have studied the properties of renal H+,K+-ATPases both in vitro and in situ. Our analysis of ion fluxes driven by a nongastric H+,K+-ATPase isoform suggests that it exchanges Na (rather than H) for K under normal circumstances. Thus, the individual H+,K+-ATPase isoforms may make diverse contributions to renal cation transport. We find that the activities of renal H+,K+-ATPases in situ are regulated by endocytosis, which is mediated by an endocytosis signal in the cytoplasmic tail of the gastric H+,K+-ATPase beta-subunit. Transgenic mice expressing a version of this protein in which the signal has been disabled show constitutively active renal K resorption. The identities of the H+,K+-ATPase isoforms that are normally subject to endocytic regulation and the nature of the participating epithelial cell machinery have yet to be established.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Grishin
authors.forename: J
authors.initials: J
authors.lastname: Reinhard
authors.forename: L A
authors.initials: LA
authors.lastname: Dunbar
authors.forename: N
authors.initials: N
authors.lastname: Courtois-Coutry
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Giebisch
authors.forename: M J
authors.initials: MJ
authors.lastname: Caplan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013270:Stomach / Q000201:enzymology*; D019459:Urothelium / Q000378:metabolism; D014882:Water-Electrolyte Balance
chemical_list: D017506:H(+)-K(+)-Exchanging ATPase