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, which has (hence the term "inwardly rectifying" referring to corresponding currents in electrophysiology, but has limited physiological relevance).[8] ROMK was identified as the pore-forming component of the mitochondrial ATP-sensitive potassium (mitoKATP) channel, known to play a critical role in cardioprotection against ischemic-reperfusion injury in the heart[9] as well as in the protection against hypoxia-induced brain injury from stroke or other ischemic attacks.
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]
Role in hypokalemia and magnesium deficiency
The 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.[12] Sgk1 kinase has also been reported to phosphorylate ROMK, resulting in an increase of channels on the apical surface of the distal tubule.[13] Sgk1 is in turn regulated by the mineralocorticoid receptor such an effect may contribute to the kaliuretic action of aldosterone.
^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. doi:10.1124/pr.57.4.11. PMID16382105. S2CID11588492.
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. doi:10.1124/pr.57.4.11. PMID16382105. S2CID11588492.
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. doi:10.1007/s00418-004-0742-5. PMID15895241. S2CID24421285.
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. doi:10.1016/j.bbrc.2008.08.076. PMID18755144.
