The role of the K+ channels. A, top). Schematic diagram of ROMK on the apical membrane of the thick ascending loop of Henle. Na+, K+ and Cl− are taken up by NKCC2, however, as luminal K+ is low, K+ must be recycled back to the lumen by ROMK. The removal K together with the activity of ClC-Kb ensures that the cell maintains a transcellular electrical potential, that in turn enables Na absorption by the paracellular pathway. Bottom, Disruption of ROMK impairs both the activity of NKCC2 and also disrupts the transcellular extracellular electrical potential. Thus, Na+ absorbtion is impaired. Note, however, that the phenotype of the ROMK knockout mice is not as severe as NKCC2 mutations, suggesting that alternative K+ influx pathways are still available68. B, top). Schematic diagram of the role of Kir4.1 on the basolateral membrane in the distal convoluted tubule. Bottom, Mutations to Kir4.1 impair moment of K+ out of the cell