A comprehensive guide to the ROMK potassium channel: form and function in health and disease

Welling, Paul A.; Ho, Kevin

doi:10.1152/ajprenal.00181.2009

Cited by 161 publications

(147 citation statements)

References 179 publications

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“…Mg 21 binds to ROMK at a specific location on its cytoplasmic surface (78)(79)(80). By binding to ROMK at this site, Mg 21 blocks the channel's pore from the inside and prevents K 1 from being secreted.…”

Section: Regulation Of Distal Tubule Potassium Transportmentioning

confidence: 99%

Distal Convoluted Tubule

Subramanya

Ellison

2014

Clinical Journal of the American Society of Nephrology

222

185

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The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice.

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Section: Regulation Of Distal Tubule Potassium Transportmentioning

confidence: 99%

Distal Convoluted Tubule

Subramanya

Ellison

2014

Clinical Journal of the American Society of Nephrology

222

185

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“…43 They are present in many cell types where they play an important role in regulation or maintenance of the cell membrane potential, such as neurons, 44 Alternative splicing generates three different ROMK isoforms (ROMK1-3) with differential expression along the nephron: ROMK2 mediates apical K þ recycling in the TAL, whilst ROMK1 and ROMK3 in the distal nephron mediate K þ secretion. 45 Regulation of ROMK activity occurs by modulating the number of channels present at the cell surface, or the activity of membrane-resident channels.…”

Section: Bartter Syndromementioning

confidence: 99%

The renal channelopathies

Loudon

Fry

2014

Ann Clin Biochem

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Specific channels permit movement of selected ions through cellular membranes, and are of vital importance in a number of physiological processes, particularly in excitable tissues such as nerve and muscle, but also in endocrine organs and in epithelial biology. Disorders of channel proteins are termed channelopathies, and their importance is increasingly recognised within medicine. In the kidney, ion channels have critical roles enabling sodium and potassium reuptake or excretion along the nephron, in magnesium homeostasis, in the control of water reabsorption in the collecting duct, and in determining glomerular permeability. In this review, we assess the channelopathies encountered in each nephron segment, and see how their molecular and genetic characterisation in the past 20-30 years has furthered our understanding of normal kidney physiology and disease processes, aids correct diagnosis and promises future therapeutic opportunities.

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“…[1][2][3] Therefore, ROMK inhibition could be potassium sparing while causing natriuresis/diuresis, which is a favorable feature for a novel diuretic and would differentiate ROMKi from conventional loop diuretics such as furosemide that cause hypokalemia. 19,20 Indeed, in our present studies, ROMKi B did not cause increased urinary K + excretion and had no effect on plasma K + concentration.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Thus, ROMK plays a critical role in the regulation of renal sodium reabsorption and the body's potassium homeostasis. Human genetic studies indicated that loss-of-function mutations in ROMK cause type II Bartter syndrome, [4][5][6] featuring polyuria, polydipsia, salt wasting, hypokalemia, alkalosis, hypercalciuria, low blood pressures, elevated plasma renin and aldosterone, and excess production of renal prostaglandins.…”

mentioning

confidence: 99%

Chronic Inhibition of Renal Outer Medullary Potassium Channel Not Only Prevented but Also Reversed Development of Hypertension and End-Organ Damage in Dahl Salt-Sensitive Rats

et al. 2017

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R enal outer medullary potassium channel (ROMK) is encoded by the KCNJ1 (potassium inwardly-rectifying channel, subfamily J, member 1) gene and expressed in the apical membranes of thick ascending limb of Henle and cortical collecting duct cells; ROMK mediates potassium recycling and facilitates sodium reabsorption through Na− cotransporter in the thick ascending limb of Henle and potassium secretion in cortical collecting duct.1-3 Thus, ROMK plays a critical role in the regulation of renal sodium reabsorption and the body's potassium homeostasis. Human genetic studies indicated that loss-of-function mutations in ROMK cause type II Bartter syndrome, 4-6 featuring polyuria, polydipsia, salt wasting, hypokalemia, alkalosis, hypercalciuria, low blood pressures, elevated plasma renin and aldosterone, and excess production of renal prostaglandins. ROMK heterozygous mutations in humans protect from the development of hypertension.7 ROMK-deficient mice exhibit a Bartter syndrome type II-like phenotype. 8,9 Heterozygous disruption of ROMK in rats is associated with reduced blood pressure and less severe renal injury.10 Furthermore, acute pharmacological intervention with a small molecule ROMK inhibitor (ROMKi) compound A evoked diuresis and natriuresis in rats and dogs, 11 which establishes the concept that ROMK inhibition represents a novel diuretic mechanism. We, therefore, hypothesize that chronic ROMK inhibition by selective small molecules would induce natriuresis and diuresis and, thereby, lower blood pressure and protect from end-organ damage in hypertensive subjects. To this end, we examined the effects of a selective and potent ROMKi B, recently synthesized by Merck & Co, Inc, 12 on systemic hemodynamics, renal function and structure, vascular function, and cardiac structure and compared the effects with those of hydrochlorothiazide (HCTZ) in 2 separate Abstract-The renal outer medullary potassium (ROMK) channel mediates potassium recycling and facilitates sodium reabsorption through the Na + /K + /2Cl − cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Evidence from the phenotype of humans and rodents with functional ROMK deficiency supports the contention that selective ROMK inhibitors (ROMKi) will represent a novel diuretic with potential of therapeutic benefit for hypertension. ROMKi have recently been synthesized by Merck & Co, Inc. The present studies were designed to examine the effects of ROMKi B on systemic hemodynamics, renal function and structure, and vascular function in Dahl salt-sensitive rats. Four experimental groups-control, high-salt diet alone; ROMKi B 3 mg·kg −1 ·d −1 ; ROMKi B 10 mg·kg −1 ·d −1 ; and hydrochlorothiazide 25 mg·kg −1 ·d −1 -were included in prophylactic (from week 1 to week 9 on high-salt diet) and therapeutic studies (from week 5 to week 9 on high-salt diet), respectively. ROMKi B produced sustained blood pressure reduction and improved renal and vascular function and histological alterations induced by a high-salt diet. ROMKi B was...

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A comprehensive guide to the ROMK potassium channel: form and function in health and disease

Cited by 161 publications

References 179 publications

Distal Convoluted Tubule

Distal Convoluted Tubule

The renal channelopathies

Chronic Inhibition of Renal Outer Medullary Potassium Channel Not Only Prevented but Also Reversed Development of Hypertension and End-Organ Damage in Dahl Salt-Sensitive Rats

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