Dimeric architecture of the human bumetanide-sensitive Na-K-Cl Co-transporter.

The primary mediator of NaCl reabsorption in the renal distal tubule is the human bumetanide-sensitive Na(+)-K(+)-2Cl(-) co-transporter (hNKCC2), located at the apical membrane of the thick ascending limb of Henle's loop. The physiologic importance of this transporter is emphasized by the tubular disorder Bartter syndrome type I, which arises from the functional impairment of hNKCC2 as a result of mutations in the SLC12A1 gene. The aim of the present study was to investigate the oligomeric state of hNKCC2 to understand further its operational mechanism.

Mutations in the human Na-K-2Cl cotransporter (NKCC2) identified in Bartter syndrome type I consistently result in nonfunctional transporters.

Bartter syndrome (BS) is a heterogeneous renal tubular disorder affecting Na-K-Cl reabsorption in the thick ascending limb of Henle's loop. BS type I patients typically present with profound hypokalemia and metabolic alkalosis. The main goal of the present study was to elucidate the functional implications of six homozygous mutations (G193R, A267S, G319R, A508T, del526N, and Y998X) in the bumetanide-sensitive Na-K-2Cl cotransporter (hNKCC2) identified in patients diagnosed with BS type I.

Functional implications of mutations in the human renal outer medullary potassium channel (ROMK2) identified in Bartter syndrome.

Bartter syndrome is an autosomal recessive heterogeneous renal tubular disorder affecting NaCl reabsorption in the thick ascending limb of Henle's loop (TAL). The aim of this study was to elucidate the functional implications of mutations in the predominant human ROMK isoform in TAL, hROMK2, involved in Bartter syndrome type II. cRNA of flag-tagged hROMK2 and eight mutants identified in seven non-related patients was expressed in Xenopus laevis oocytes.