Genetic disorders of NaCl transport in the distal convoluted tubule.
The distal convoluted tubule (DCT) reabsorbs 5-10% of filtered Na, and is an important site for regulation of Na balance. Additionally, the amount and composition of the tubular fluid that leaves the DCT affects H and K secretion in more distal nephrin segments. Mutations in five genes whose products are expressed in the DCT demonstrate these points and help to define the mechanisms by which the DCT contributes to control of electrolyte balance and volume. Loss of function mutations in the apical thiazide-sensitive NaCl cotransporter and the basolateral K channel Kir4.1, and activating mutations in the Ca-sensing receptor cause a phenotypically similar salt wasting syndrome. Mutation in two recently identified kinases, WNK1 and WNK4 cause a salt-retaining syndrome through increased apical expression of NaCl cotransporter. Recent studies indicate that these genes are important not only for understanding the physiology of the distal nephron, but that they and others may also contribute to blood pressure variation in the general population.
Case-Western Reserve University, Louis Stokes VAMC, Ramelkamp Center for Research and Education, MetroHealth Medical Center, Cleveland, Ohio, USA.
R Tyler
RT
Miller
D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008138:Loop of Henle / Q000503:physiopathology*; D008957:Models, Genetic; D012964:Sodium / Q000378:metabolism*; D049992:Sodium Chloride Symporters / Q000235:genetics*
D049992:Sodium Chloride Symporters; D012964:Sodium