Renal outer medullary potassium channel knockout models reveal thick ascending limb function and dysfunction.
The renal outer medullary potassium channel (ROMK) is an adenosine triphosphate-sensitive inward-rectifier potassium channel (Kir1.1 or KCNJ1) highly expressed in the cortical and medullary thick ascending limbs (TAL), connecting segment (CNT) and cortical collecting duct (CCD) in the mammalian kidney, where it serves to recycle potassium (K(+)) across the apical membrane in TAL and to secrete K(+) in the CNT and CCD. ROMK channel mutations cause type II Bartter's syndrome with salt wasting and dehydration, and ROMK knockout mice display a similar phenotype of Bartter's syndrome in humans. Studies from ROMK null mice indicate that ROMK is required to form both the small-conductance (30pS, SK) K channels and the 70pS (IK) K channels in the TAL. The availability of ROMK(-/-) mice has made it possible to study electrolyte transport along the nephron in order to understand the TAL function under physiological conditions and the compensatory mechanisms of salt and water transport under the conditions of TAL dysfunction. This review summarizes previous progress in the study of K(+) channel activity in the TAL and CCD, ion transporter expression and activities along the nephron, and renal functions under physiological and pathophysiological conditions using ROMK(-/-) mice.
Department of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8026, USA. tong.wang@yale.edu
Tong
T
Wang
D000818:Animals; D007686:Kidney Tubules, Distal / Q000502:physiology; D008138:Loop of Henle / Q000502:physiology* / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D012965:Sodium Chloride / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1
C510693:Kcnj1 protein, mouse; D024661:Potassium Channels, Inwardly Rectifying; C578714:SLC12A1 protein, human; C578715:Slc12a1 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D012965:Sodium Chloride; D011188:Potassium