The renal outer medullary potassium channel (ROMK) is an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb (TAL) and potassium secretion in the cortical collecting duct (CCD) of the nephron. In humans, ROMK is encoded by the KCNJ1 (potassium inwardly-rectifying channel, subfamily J, member 1) gene.[5][6][7] Multiple transcript variants encoding different isoforms have been found for this gene.[8]
Function
Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is inhibited by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell (hence the term "inwardly rectifying"). ROMK was identified as the pore forming component of mitoKATP channels that are known to have a critical role during stroke or other ischemic attacks in the protection against hypoxia-induced brain injury.[8][9]
Clinical significance
Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure.[8]
^Yano H, Philipson LH, Kugler JL, Tokuyama Y, Davis EM, Le Beau MM, Nelson DJ, Bell GI, Takeda J (May 1994). "Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA". Mol. Pharmacol. 45 (5): 854–60. PMID8190102.
^Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol. Rev. 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID16382105.
Kubo Y, Adelman JP, Clapham DE, et al. (2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol. Rev. 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID16382105.
Brochard K, Boyer O, Blanchard A, et al. (2009). "Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome". Nephrol. Dial. Transplant. 24 (5): 1455–64. doi:10.1093/ndt/gfn689. PMID19096086.
Nüsing RM, Pantalone F, Gröne HJ, et al. (2005). "Expression of the potassium channel ROMK in adult and fetal human kidney". Histochem. Cell Biol. 123 (6): 553–9. doi:10.1007/s00418-004-0742-5. PMID15895241.
Nozu K, Fu XJ, Kaito H, et al. (2007). "A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism". Pediatr. Nephrol. 22 (8): 1219–23. doi:10.1007/s00467-007-0468-4. PMID17401586.
Lin D, Kamsteeg EJ, Zhang Y, et al. (2008). "Expression of tetraspan protein CD63 activates protein-tyrosine kinase (PTK) and enhances the PTK-induced inhibition of ROMK channels". J. Biol. Chem. 283 (12): 7674–81. doi:10.1074/jbc.M705574200. PMID18211905.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Yoo D, Kim BY, Campo C, et al. (2003). "Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A.". J. Biol. Chem. 278 (25): 23066–75. doi:10.1074/jbc.M212301200. PMID12684516.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Nanazashvili M, Li H, Palmer LG, et al. (2007). "Moving the pH gate of the Kir1.1 inward rectifier channel". Channels (Austin). 1 (1): 21–8. doi:10.4161/chan.3707. PMID19170254.
Yoo D, Flagg TP, Olsen O, et al. (2004). "Assembly and trafficking of a multiprotein ROMK (Kir 1.1) channel complex by PDZ interactions". J. Biol. Chem. 279 (8): 6863–73. doi:10.1074/jbc.M311599200. PMID14604981.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Tobin MD, Tomaszewski M, Braund PS, et al. (2008). "Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population". Hypertension. 51 (6): 1658–64. doi:10.1161/HYPERTENSIONAHA.108.112664. PMID18443236.
Murthy M, Cope G, O'Shaughnessy KM (2008). "The acidic motif of WNK4 is crucial for its interaction with the K channel ROMK". Biochem. Biophys. Res. Commun. 375 (4): 651–4. doi:10.1016/j.bbrc.2008.08.076. PMID18755144.
Welling, P. A.; Ho, K. (20 May 2009). "A comprehensive guide to the ROMK potassium channel: form and function in health and disease". AJP: Renal Physiology. 297 (4): F849–F863. doi:10.1152/ajprenal.00181.2009.
