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. Multiple transcript variants encoding different isoforms have been found for this gene.
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.
Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure.
Role in hypokalemia and magnesium deficiency
ROMK channels are inhibited by magnesium in the nephron's normal physiologic state. In states of hypokalemia (a state of potassium deficiency), concurrent magnesium deficiency results in a state of hypokalemia that may be more difficult to correct with potassium replacement alone. This may be directly due to decreased inhibition of the outward potassium current in states where magnesium is low. Conversely, magnesium deficiency alone is not likely to cause a state of hypokalemia .
^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". Molecular Pharmacology. 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". Pharmacological Reviews. 57 (4): 509–26. PMID16382105. doi:10.1124/pr.57.4.11.
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". Pharmacological Reviews. 57 (4): 509–26. PMID16382105. doi:10.1124/pr.57.4.11.
Brochard K, Boyer O, Blanchard A, Loirat C, Niaudet P, Macher MA, Deschenes G, Bensman A, Decramer S, Cochat P, Morin D, Broux F, Caillez M, Guyot C, Novo R, Jeunemaître X, Vargas-Poussou R (May 2009). "Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome". Nephrology, Dialysis, Transplantation. 24 (5): 1455–64. PMID19096086. doi:10.1093/ndt/gfn689.
Nüsing RM, Pantalone F, Gröne HJ, Seyberth HW, Wegmann M (June 2005). "Expression of the potassium channel ROMK in adult and fetal human kidney". Histochemistry and Cell Biology. 123 (6): 553–9. PMID15895241. doi:10.1007/s00418-004-0742-5.
Nozu K, Fu XJ, Kaito H, Kanda K, Yokoyama N, Przybyslaw Krol R, Nakajima T, Kajiyama M, Iijima K, Matsuo M (August 2007). "A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism". Pediatric Nephrology. 22 (8): 1219–23. PMID17401586. doi:10.1007/s00467-007-0468-4.
Lin D, Kamsteeg EJ, Zhang Y, Jin Y, Sterling H, Yue P, Roos M, Duffield A, Spencer J, Caplan M, Wang WH (March 2008). "Expression of tetraspan protein CD63 activates protein-tyrosine kinase (PTK) and enhances the PTK-induced inhibition of ROMK channels". The Journal of Biological Chemistry. 283 (12): 7674–81. PMID18211905. doi:10.1074/jbc.M705574200.
Yoo D, Kim BY, Campo C, Nance L, King A, Maouyo D, Welling PA (June 2003). "Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A". The Journal of Biological Chemistry. 278 (25): 23066–75. PMID12684516. doi:10.1074/jbc.M212301200.
Yoo D, Flagg TP, Olsen O, Raghuram V, Foskett JK, Welling PA (February 2004). "Assembly and trafficking of a multiprotein ROMK (Kir 1.1) channel complex by PDZ interactions". The Journal of Biological Chemistry. 279 (8): 6863–73. PMID14604981. doi:10.1074/jbc.M311599200.
Tobin MD, Tomaszewski M, Braund PS, Hajat C, Raleigh SM, Palmer TM, Caulfield M, Burton PR, Samani NJ (June 2008). "Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population". Hypertension. 51 (6): 1658–64. PMID18443236. doi:10.1161/HYPERTENSIONAHA.108.112664.
Murthy M, Cope G, O'Shaughnessy KM (October 2008). "The acidic motif of WNK4 is crucial for its interaction with the K channel ROMK". Biochemical and Biophysical Research Communications. 375 (4): 651–4. PMID18755144. doi:10.1016/j.bbrc.2008.08.076.
Welling PA, Ho K (October 2009). "A comprehensive guide to the ROMK potassium channel: form and function in health and disease". American Journal of Physiology. Renal Physiology. 297 (4): F849–63. PMID19458126. doi:10.1152/ajprenal.00181.2009.