Fig. 3

Schematic of localizations and function of ion transporters defective in Bartter Syndrome and Pseudo-Bartter conditions. ClC-kb is mainly found in the thick ascending loop of Henle (TAL), (a) and distal tubules (DCT), (b) of kidneys, SLC26A3 in the intestine (c), Pendrin localizes mainly to renal beta-intercalated cells (d), CFTR is found in all nephron segments (e), and 11β-HSD2 enzyme in cortical collecting duct (f). (a) Thick ascending loop of Henle: Luminal NKCC2 enables import of Na+, K+ and Cl- into the cells. K+ flows back to the lumen through ROMK1 channels; Na+ and Cl- are reabsorbed to the blood stream through Na+/K+ ATPase and ClC-kb channels. CASR inhibits the luminal ROMK channel which in turn results in decreased NaCl reabsorption and increased urinary Cl-. (b) Distal Tubulus: Cl- transport occurs via the luminal, NCCT and exit to blood by ClC-kb. (c) In enterocytes, Cl- absorbed from the intestinal lumen via SLC26A3 and transported to the interstitium by ClC-2. Na+ enters the cell via ENaC channels or Na+/ H+ exchangers and is transported to the interstitium by the Na+/k+ ATPase. (d) Penderin participates in urinary bicarbonate excretion with tubular Cl- reabsorption. (e) CFTR functions as a Cl- channel and CFTR functions influences other ion channels such as ENaC and ROMK in the cortex and medulla. (f) mineralocorticoid aldosteron binds to Mineralcorticoid receptors (MR) which in turn binds to the hormone response elements (HRE) in the nucleus and stimulates increased resorption of Na+ from the urine through transcription of genes involved in ENac and Na+/K+ ATP channels. Simultaneously glucocorticoid cortisol oxidized to inactive cortisone by 11β-HSD2 enzyme