Abstract
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.
Similar content being viewed by others
References
Lee WS, Hebert SC. ROMK inwardly rectifying ATP-sensitive K+ channel. I. Expression in rat distal nephron segments. Am J Physiol. 1995;268(6 Pt 2):F1124–31.
Ashcroft SJH, Ashcroft FM. Properties and functions of ATP-sensitive K-channels. Cell Signal. 1990;2:197–214.
Ashcroft SJ, Ashcroft FM. The sulfonylurea receptor. Biochim Biophys Acta. 1992;1175(1):45–59.
Misler S, Giebisch G. ATP-sensitive potassium channels in physiology, pathophysiology, and pharmacology. Curr Opin Nephrol Hypertens. 1992;1(1):21–33.
Wang T, Wang WH, Klein-Robbenhaar G, Giebisch G. Effects of glyburide on renal tubule transport and potassium-channel activity. Ren Physiol Biochem. 1995;18(4):169–82.
Wang T, Wang WH, Klein-Robbenhaar G, Giebisch G. Effects of a novel KATP channel blocker on renal tubule function and K channel activity. J Pharmacol Exp Ther. 1995;273(3):1382–9.
Wang T. The effects of potassium channel opener minoxidil on renal electrolytes transport in the loop of Henle. J Pharmacol Exp Ther. 2003;304(2):833–40.
Hebert SC, Desir G, Giebisch G, Wang W. Molecular diversity and regulation of renal potassium channels. Physiol Rev. 2005;85(1):319–71.
Lu M, Wang W. Two types of K+ channels are present in the apical membrane of the thick ascending limb of the mouse kidney. Kidney Blood Press Res. 2000;23:75–82.
Lu M, Wang T, Yan Q, et al. Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter’s) knockout mice. J Biol Chem. 2002;277(40):37881–7.
Lu M, Wang T, Yan Q, Wang W, Giebisch G, Hebert SC. ROMK is required for expression of the 70-pS K channel in the thick ascending limb. Am J Physiol Renal Physiol. 2004;286(3):F490–5.
Lorenz JN, Baird NR, Judd LM, et al. Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter’s syndrome. J Biol Chem. 2002;277(40):37871–80.
Yan Q, Yang X, Cantone A, Giebisch G, Hebert S, Wang T. Female ROMK null mice manifest more severe Bartter II phenotype on renal function and higher PGE2 production. Am J Physiol Regul Integr Comp Physiol. 2008;295(3):R997–1004.
Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP. Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na–K–2Cl cotransporter NKCC2. Nat Genet. 1996;13(2):183–8.
Hebert SC. Bartter syndrome. Curr Opin Nephrol Hypertens. 2003;12(5):527–32.
Gu R, Wei Y, Jiang H, Balazy M, Wang W. Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL. Am J Physiol Renal Physiol. 2001;280(2):F223–30.
Hebert SC, Gullans SR. The electroneutral sodium–(potassium)–chloride co-transporter family: a journey from fish to the renal co-transporters. Curr Opin Nephrol Hypertens. 1995;4(5):389–91.
Giebisch G, Klein-Robbenhaar G, Klein-Robbenhaar J, Ratheiser K, Unwin R. Renal and extrarenal sites of action of diuretics. Cardiovasc Drugs Ther. 1993;7(Suppl 1):11–21.
Cantone A, Yang X, Yan Q, Giebisch G, Hebert SC, Wang T. Mouse model of type II Bartter’s syndrome. I. Upregulation of thiazide-sensitive Na–Cl cotransport activity. Am J Physiol Renal Physiol. 2008;294(6):F1366–72.
Plata C, Meade P, Hall A, et al. Alternatively spliced isoform of apical Na(+)–K(+)–Cl(−) cotransporter gene encodes a furosemide-sensitive Na(+)–Cl(−) cotransporter. Am J Physiol Renal Physiol. 2001;280(4):F574–82.
Takahashi N, Chernavvsky DR, Gomez RA, Igarashi P, Gitelman HJ, Smithies O. Uncompensated polyuria in a mouse model of Bartter’s syndrome. Proc Natl Acad Sci USA. 2000;97(10):5434–9.
Frindt G, Palmer LG. Apical potassium channels in the rat connecting tubule. Am J Physiol Renal Physiol. 2004;287(5):F1030–7.
Gray DA, Frindt G, Palmer LG. Quantification of K+ secretion through apical low-conductance K channels in the CCD. Am J Physiol Renal Physiol. 2005;289(1):F117–26.
Malnic G, Klose RM, Giebisch G. Micropuncture study of renal potassium excretion in the rat. Am J Physiol. 1964;206:674–86.
Wang WH. Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects. Am J Physiol Renal Physiol. 2006;290(1):F14–9.
Bailey MA, Cantone A, Yan Q, et al. Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter’s syndrome and in adaptation to a high-K diet. Kidney Int. 2006;70(1):51–9.
Hunter M, Lopes AG, Boulpaep EL, Giebisch GH. Single channel recordings of calcium-activated potassium channels in the apical membrane of rabbit cortical collecting tubules. Proc Natl Acad Sci USA. 1984;81(13):4237–9.
Pacha J, Frindt G, Sackin H, Palmer LG. Apical maxi K channels in intercalated cells of CCT. Am J Physiol. 1991;261(4 Pt 2):F696–705.
Liu W, Xu S, Woda C, Kim P, Weinbaum S, Satlin LM. Effect of flow and stretch on the [Ca2+]i response of principal and intercalated cells in cortical collecting duct. Am J Physiol Renal Physiol. 2003;285(5):F998–1012.
Satlin LM. Developmental regulation of expression of renal potassium secretory channels. Curr Opin Nephrol Hypertens. 2004;13(4):445–50.
Woda CB, Bragin A, Kleyman TR, Satlin LM. Flow-dependent K+ secretion in the cortical collecting duct is mediated by a maxi-K channel. Am J Physiol Renal Physiol. 2001;280(5):F786–93.
Wagner CA, Loffing-Cueni D, Yan Q, et al. Mouse model of type II Bartter’s syndrome. II. Altered expression of renal sodium- and water-transporting proteins. Am J Physiol Renal Physiol. 2008;294(6):F1373–80.
Wang T, Yang CL, Abbiati T, et al. Mechanism of proximal tubule bicarbonate absorption in NHE3 null mice. Am J Physiol. 1999;277(2 Pt 2):F298–302.
Wang T, Yang CL, Abbiati T, Shull GE, Giebisch G, Aronson PS. Essential role of NHE3 in facilitating formate-dependent NaCl absorption in the proximal tubule. Am J Physiol Renal Physiol. 2001;281(2):F288–92.
Abdallah JG, Schrier RW, Edelstein C, Jennings SD, Wyse B, Ellison DH. Loop diuretic infusion increases thiazide-sensitive Na(+)/Cl(−)-cotransporter abundance: role of aldosterone. J Am Soc Nephrol. 2001;12(7):1335–41.
Reilly RF, Ellison DH. Mammalian distal tubule: physiology, pathophysiology, and molecular anatomy. Physiol Rev. 2000;80(1):277–313.
Na KY, Oh YK, Han JS, et al. Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats. Am J Physiol Renal Physiol. 2003;284(1):F133–43.
Acknowledgment
This work was supported by grants from the National Institute of Health RO1 DK 54999 and P01 DK 17433. The review is dedicated to the memory of Dr. Steve S. Hebert for his contributions to renal physiology.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Wang, T. Renal outer medullary potassium channel knockout models reveal thick ascending limb function and dysfunction. Clin Exp Nephrol 16, 49–54 (2012). https://doi.org/10.1007/s10157-011-0495-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10157-011-0495-0