title: Developmental maturation of Na(+)-H+ exchange in rat renal tubular brush-border membrane.
abstract: The developmental maturation of the Na(+)-H+ exchanger present in the proximal tubular luminal membrane of the rat was investigated. An overshoot of 1 mM Na+ uptake was evident in brush-border membrane vesicles derived from the renal cortex of 7- and 21-day-old and adult rats in the presence of an outwardly directed H+ concentration ([H+]) gradient [intravesicular pH (pHi) = 5.5; extravesicular pH (pHo) = 7.5]. Na+ uptake was amiloride sensitive at all ages examined. Significantly higher initial rate (3 s) Na+ uptake and peak accumulation (60 s) in the presence of a [H+] gradient were found in vesicles from 7-day-old rats compared with adult animals. Significantly enhanced initial rate Na+ uptake by neonatal vesicles was also evident under pH-equilibrated conditions (pHi = pHo = 7.5). An age-related decrease in amiloride-sensitive Na+ accumulation by vesicles was found. Kinetic analysis of Na(+)-H+ exchange in voltage-clamped vesicles, in the presence of dimethylamiloride (DMA), and calculating 5-s Na+ uptake values showed a maturational decrease in capacity (decreasing Vmax) coupled with a maturational increase in affinity (decreasing Km) of Na(+)-H+ antiport. These data suggest that an enhanced amiloride-inhibitable Na(+)-H+ exchange activity due to increased capacity of exchange exists in the proximal tubular luminal membrane of the neonatal rat. This increased Na(+)-H+ exchange may potentially contribute to positive Na+ balance in the growing organism and may rapidly dissipate the electrochemical Na+ gradient across the luminal membrane necessary for Na(+)-solute contransport, thereby contributing to glycosuria and aminoaciduria of early life.
authors.affiliation: Department of Pediatrics, University of Washington, School of Medicine, Seattle 98105.
authors.forename: I
authors.initials: I
authors.lastname: Zelikovic
authors.forename: E
authors.initials: E
authors.lastname: Stejskal
authors.forename: P
authors.initials: P
authors.lastname: Lohstroh
authors.forename: A
authors.initials: A
authors.lastname: Budreau
authors.forename: R W
authors.initials: RW
authors.lastname: Chesney
mesh_terms: D000375:Aging / Q000378:metabolism*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007684:Kidney Tubules / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
chemical_list: D002352:Carrier Proteins; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D012964:Sodium