Figure 1214

Transport systems involved in transepithelial sodium-chloride transport in the thick ascending limb (TAL). Clinical data suggest that the primary defect in the antenatal and classic Bartter syndrome variants involves impaired sodium chloride transport in the TAL. Under normal physiologic conditions, sodium chloride is transported across the apical membrane by way of the bumetanide-sensitive sodium-potassium-2chloride (Na-K-2Cl) cotransporter (NKCC2). This electroneutral transporter is driven by the low intracellular sodium and chloride concentrations generated by the sodium-potassium pump and the basolateral chloride channels and potassium-chloride cotransporter. In addition, apical potassium recycling by way of the low-conductance potassium channel (ROMK) ensures the efficient functioning of the Na-K-2Cl cotransporter. The activity of the ROMK channel, in turn, is regulated by a number of cell messengers, eg, calcium (Ca2+) and adenosine triphosphate (ATP), as well as by the calcium-sensing receptor (CaR), prostaglandin EP3 receptor, and vasopressin receptor (V2R) by way of cAMP-dependent pathways and arachidonic acid (AA) metabolites, eg, 20-hydroxy-eicosatetraenoic acid (20-HETE). The positive transluminal voltage (Vte) drives the paracellular reabsorption of calcium ions and magnesium ions (Mg2+) [25]. cAMP—cyclic adenosine monophosphate; PGE2— prostaglandin E2; PKA—protein kinase A.

Defective

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