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Gene Review

Kcnj1  -  potassium inwardly-rectifying channel,...

Mus musculus

Synonyms: ATP-regulated potassium channel ROM-K, ATP-sensitive inward rectifier potassium channel 1, Inward rectifier K(+) channel Kir1.1, Kir1.1, Potassium channel, inwardly rectifying subfamily J member 1, ...
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Disease relevance of Kcnj1

  • The surviving ROMK null mice have normal gross renal morphology with no evidence of significant hydronephrosis, whereas non-surviving null mice exhibit marked hydronephrosis [1].
  • ROMK-deficient mice that survived beyond weaning grew to adulthood; however, they had metabolic acidosis, elevated blood concentrations of Na(+) and Cl(-), reduced blood pressure, polydipsia, polyuria, and poor urinary concentrating ability [2].
  • However, the mechanism of renal K(+) wasting and hypokalemia that develop in individuals with ROMK Bartter's syndrome is not apparent given the proposed loss of the collecting duct SK channel [1].
  • It is likely that ROMK forms a critical subunit of the 70-pS K channel, accounting for the loss of apical K secretory channel activity in ROMK Bartter syndrome [3].
  • Loss-of-function mutations in the K channel, ROMK (Kir1.1; KCNJ1), cause Bartter syndrome, a genetically heterogeneous disorder characterized by severe reduction in salt absorption by the TAL, Na wasting, polyuria, and hypokalemic alkalosis [3].

High impact information on Kcnj1

  • By expression in Xenopus laevis oocytes, we show that WNK4 also inhibits the renal K+ channel ROMK [4].
  • This inhibition is independent of WNK4 kinase activity and is mediated by clathrin-dependent endocytosis of ROMK, mechanisms distinct from those that characterize WNK4 inhibition of NCCT [4].
  • CFTR has been proposed as a regulator of the 30 pS, ATP-sensitive renal K channel (Kir1.1, also known as renal outer medullar K [ROMK]) that is critical for K secretion by cells of the thick ascending limb (TAL) and distal nephron segments responsive to aldosterone [5].
  • In contrast, surface expression and macroscopic current density was augmented by a phosphorylation mimic mutation, Kir1.1 S44D [6].
  • The Kir1.1 (ROMK) subtypes of inward rectifier K+ channels mediate potassium secretion and regulate sodium chloride reabsorption in the kidney [6].

Biological context of Kcnj1

  • To understand better the pathogenesis of type II Bartter's syndrome, we developed a mouse lacking ROMK and examined its phenotype [2].
  • ROMK null mice were polyuric and natriuretic with an elevated hematocrit consistent with mild extracellular volume depletion [1].
  • At a membrane potential of -60 mV, both IRK and ROMK had single-exponential open-time distributions, with mean open times of 279 +/- 58 ms (n = 4) for IRK1 and 23 +/- 1 ms (n = 7) for ROMK [7].

Anatomical context of Kcnj1

  • Removal of the phosphorylation site by point mutation (Kir1.1, S44A) dramatically attenuated the macroscopic current density in Xenopus oocytes [6].
  • The expression of ROMK channels in the plasma membrane is regulated by protein tyrosine kinase (PTK), serum and glucorticoid-induced kinase (SGK), and with-no-lysine-kinase 4 [8].
  • The decreased surface expression of ROMK caused by mutant WNK4 was postulated to be a mechanism for decreased potassium secretion in distal nephrons that would presumably lead to hyperkalemia [9].
  • We show that potassium absorption in the loop of Henle is reduced in Romk-deficient mice and can account for a significant fraction of renal potassium loss [10].

Associations of Kcnj1 with chemical compounds

  • Despite loss of ROMK expression, the normokalemic null mice exhibited significantly increased kaliuresis, indicating alternative mechanisms for K(+) absorption/secretion in the nephron [1].
  • Increases in superoxide anions induced by low dietary K intake are responsible for the stimulation of PTK expression and tyrosine phosphorylation of ROMK channels [8].
  • 1. TNP-ATP binding was specific for the COOH termini of K(ATP) channels because this nucleotide did not bind to the NH(2) termini of Kir1.1 or Kir6 [11].
  • Introduction of an arginine at this position in Kir1.1 channels rendered the N-terminal PIP(2) site functional largely increasing the PIP(2) affinity [12].
  • Competition of TNP-ATP binding to the Kir1.1 COOH terminus by MgATP was complex with both Mg(2+) and MgATP effects [11].

Other interactions of Kcnj1

  • In contrast, Kir1.1 and Kir2.1 channels were insensitive to ethanol and various SSRIs and antipsychotics, although thioridazine weakly inhibited Kir1.1 channels [13].
  • Systematic constructions of chimerical Kir6.2-Kir1.1 channels indicated that full pH sensitivity required the N terminus, C terminus, and M2 region [14].
  • These currents were insensitive to tolbutemide, a selective blocker of Kir6.x channels, and to tertiapin, a blocker for Kir1.1 and Kir3.1/3.4 channels [15].

Analytical, diagnostic and therapeutic context of Kcnj1

  • Western blotting also revealed the presence of the 40 kD ROMK protein using an anti-ROMK antibody [16].
  • Here, we used free-flow micropuncture and stationary microperfusion of the late distal tubule to explore the mechanism of renal potassium wasting in the Romk-deficient, Type II Bartter's mouse [10].


  1. 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. Lu, M., Wang, T., Yan, Q., Yang, X., Dong, K., Knepper, M.A., Wang, W., Giebisch, G., Shull, G.E., Hebert, S.C. J. Biol. Chem. (2002) [Pubmed]
  2. Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome. Lorenz, J.N., Baird, N.R., Judd, L.M., Noonan, W.T., Andringa, A., Doetschman, T., Manning, P.A., Liu, L.H., Miller, M.L., Shull, G.E. J. Biol. Chem. (2002) [Pubmed]
  3. ROMK is required for expression of the 70-pS K channel in the thick ascending limb. Lu, M., Wang, T., Yan, Q., Wang, W., Giebisch, G., Hebert, S.C. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  4. WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion. Kahle, K.T., Wilson, F.H., Leng, Q., Lalioti, M.D., O'Connell, A.D., Dong, K., Rapson, A.K., MacGregor, G.G., Giebisch, G., Hebert, S.C., Lifton, R.P. Nat. Genet. (2003) [Pubmed]
  5. CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. Lu, M., Leng, Q., Egan, M.E., Caplan, M.J., Boulpaep, E.L., Giebisch, G.H., Hebert, S.C. J. Clin. Invest. (2006) [Pubmed]
  6. Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A. Yoo, D., Kim, B.Y., Campo, C., Nance, L., King, A., Maouyo, D., Welling, P.A. J. Biol. Chem. (2003) [Pubmed]
  7. Structural determinants of gating in inward-rectifier K+ channels. Choe, H., Palmer, L.G., Sackin, H. Biophys. J. (1999) [Pubmed]
  8. Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects. Wang, W.H. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  9. Apical localization of renal K channel was not altered in mutant WNK4 transgenic mice. Yamauchi, K., Yang, S.S., Ohta, A., Sohara, E., Rai, T., Sasaki, S., Uchida, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  10. 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. Bailey, M.A., Cantone, A., Yan, Q., MacGregor, G.G., Leng, Q., Amorim, J.B., Wang, T., Hebert, S.C., Giebisch, G., Malnic, G. Kidney Int. (2006) [Pubmed]
  11. The carboxyl termini of K(ATP) channels bind nucleotides. Vanoye, C.G., MacGregor, G.G., Dong, K., Tang, L., Buschmann, A.S., Hall, A.E., Lu, M., Giebisch, G., Hebert, S.C. J. Biol. Chem. (2002) [Pubmed]
  12. Phosphatidylinositol 4,5-bisphosphate (PIP2) modulation of ATP and pH sensitivity in Kir channels. A tale of an active and a silent PIP2 site in the N terminus. Schulze, D., Krauter, T., Fritzenschaft, H., Soom, M., Baukrowitz, T. J. Biol. Chem. (2003) [Pubmed]
  13. Modulators of G protein-activated inwardly rectifying K+ channels: potentially therapeutic agents for addictive drug users. Kobayashi, T., Washiyama, K., Ikeda, K. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  14. Requirement of multiple protein domains and residues for gating K(ATP) channels by intracellular pH. Piao, H., Cui, N., Xu, H., Mao, J., Rojas, A., Wang, R., Abdulkadir, L., Li, L., Wu, J., Jiang, C. J. Biol. Chem. (2001) [Pubmed]
  15. Functional expression of Kir4.1 channels in spinal cord astrocytes. Olsen, M.L., Higashimori, H., Campbell, S.L., Hablitz, J.J., Sontheimer, H. Glia (2006) [Pubmed]
  16. Cyclosporine stimulates Na+-K+-Cl- cotransport activity in cultured mouse medullary thick ascending limb cells. Wu, M.S., Yang, C.W., Bens, M., Peng, K.C., Yu, H.M., Vandewalle, A. Kidney Int. (2000) [Pubmed]
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