ROMK

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). 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 as well as in the protection against hypoxia-induced brain injury from stroke or other ischemic attacks.

Klotho is a beta-glucuronidase-like enzyme that activates ROMK by removal of sialic acid.

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.

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. Sgk1 kinase has also been reported to phosphorylate ROMK, resulting in an increase of channels on the apical surface of the distal tubule. Sgk1 is in turn regulated by the mineralocorticoid receptor such an effect may contribute to the kaliuretic action of aldosterone.

References

References

1. (March 1993). "Cloning and expression of an inwardly rectifying ATP-regulated potassium channel". Nature.
2. (May 1994). "Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA". Molecular Pharmacology.
3. (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews.
4. "Entrez Gene: potassium inwardly-rectifying channel".
5. (August 2012). "Mitochondrial ROMK channel is a molecular component of mitoK(ATP)". Circulation Research.
6. (2008). "Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1". [[Proceedings of the National Academy of Sciences of the United States of America]].
7. Huang CL. (2010). "Regulation of ion channels by secreted Klotho: mechanisms and implications". [[Kidney International]].
8. (October 2007). "Mechanism of hypokalemia in magnesium deficiency". Journal of the American Society of Nephrology.
9. (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.