Expression of the β2-subunit and apical localization of Na+-K+-ATPase in metanephric kidney

During kidney organogenesis, the Na+-K+-ATPase pump is not restricted to the basolateral plasma membrane of the renal epithelial cell but is instead either localized to the apical and lateral membrane sites of the early nephron or expressed in a nonpolarized distribution in the newly formed collecting ducts. The importance of Na+-K+-ATPase beta-subunit expression in the translocation of the Na+-K+-ATPase to the plasma membrane raises the question as to which beta-subunit isoform is expressed during kidney organogenesis. Immunocytochemical, Western analysis and RNase protection studies showed that both beta 1-subunit protein and beta 2 mRNA are expressed in the early gestation to midgestation human metanephric kidney. In contrast, although beta 1 mRNA abundance is equivalent to that of the beta 2-subunit in the metanephric kidney, the beta 1-subunit protein was not detected in early to midgestation metanephric kidney samples. Immunocytochemical analysis revealed that both alpha 1- and beta 2-subunits were present in the apical epithelial plasma membranes of distal nephron segments of early stage nephrons, maturing loops of Henle, and collecting ducts during kidney development. We also detected a significant increase in alpha 1 and beta 1 mRNA after birth with a marked reduction in beta 2 mRNA abundance associated with an increase in alpha 1- and beta 1-subunit proteins and loss of beta 2 protein expression. These studies support the conclusion that the expression of the beta 2-subunit in the fetal kidney may be an important mechanism controlling polarization of the Na+-K+-ATPase pump in the epithelia of the developing nephron during kidney organogenesis.