Potassium-related inherited tubulopathies

Landau, Daniel

doi:10.1007/s00018-006-6011-0

Cited by 24 publications

(11 citation statements)

References 37 publications

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“…[9][10][11] The aforementioned difference in potassium disturbance has been attributed to postnatal maturation of nephron transporter expression. 26,27 Our findings, together with results from mice 15,16 and humans, [25][26][27] strongly suggest that ROMK may play a crucial role in the development of potassium secretion after birth. 28,29 Alternative potassium secretion pathways or mechanisms reducing plasma potassium level may develop later in life.…”

Section: Discussionsupporting

confidence: 60%

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Heterozygous Disruption of Renal Outer Medullary Potassium Channel in Rats Is Associated With Reduced Blood Pressure

et al. 2013

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H ypertension is one of the most common chronic diseases with complex pathogenesis. It is likely that hypertension is a consequence of an interaction between genetic and environmental factors. Although genome-wide association studies have identified multiple genes that are associated with hypertension, a great deal of our current understanding of the molecular mechanisms involved in blood pressure (BP) regulation 1 has come from analysis of the genes responsible for monogenetic syndromes of hypertension and hypotension. For example, loss-of-function mutations in the Na + /Cl − cotransporter (NCC; SLC12A3) causes Gitelman syndrome: patients are either normotensive or hypotensive with hypochloremic metabolic alkalosis and hypokalemia. [2][3][4][5] Increased NCC membrane expression resulting from either gain-of-function mutations with-no-lysine kinase 1 or loss-offunction mutations with-no-lysine kinase 4 leads to Gordon syndrome, characterized by salt-sensitive (SS) hypertension, hyperkalemia, and metabolic acidosis. 6,7 Loss-of-function mutations in Na− cotransporter (NKCC2, SLC12A1) or renal outer medullary potassium channel (ROMK, KCNJ1) are responsible for Bartter syndrome type I and type II, respectively. [8][9][10][11] These disorders are characterized by polyuria, salt wasting, hypokalemia, metabolic alkalosis, hypercalciuria, and hypotension. Furthermore, Ji et al 12 demonstrated that heterozygous mutations in all 3 of these genes, SLC12A3, SLC12A1, and KCNJ1, are associated with clinically significant BP reduction and protection from development of hypertension. Thus, these syndromes further underscore a key role of renal Abstract-The renal outer medullary potassium channel (ROMK, KCNJ1) 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. Human genetic studies indicate that ROMK homozygous loss-of-function mutations cause type II Bartter syndrome, featuring polyuria, renal salt wasting, and hypotension; humans heterozygous for ROMK mutations identified in the Framingham Heart Study have reduced blood pressure. ROMK null mice recapitulate many of the features of type II Bartter syndrome. We have generated an ROMK knockout rat model in Dahl salt-sensitive background by using zinc finger nuclease technology and investigated the effects of knocking out ROMK on systemic and renal hemodynamics and kidney histology in the Dahl salt-sensitive rats. The ROMK −/− pups recapitulated features identified in the ROMK null mice. The ROMK +/− rats, when challenged with a 4% salt diet, exhibited a reduced blood pressure compared with their ROMK +/+ littermates. More importantly, when challenged with an 8% salt diet, the Dahl salt-sensitive rats with 50% less ROMK expression showed increased protection from salt-induced blood pressure elevation and signs of protection from renal injury. Our findings in ROMK knockout Dahl salt-sensitive rats, together with the previous reports in humans and m...

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Section: Discussionsupporting

confidence: 60%

“…26,27 Our findings, together with results from mice 15,16 and humans, 25-27 strongly suggest that ROMK may play a crucial role in the development of potassium secretion after birth.…”

Section: Discussionsupporting

confidence: 57%

Heterozygous Disruption of Renal Outer Medullary Potassium Channel in Rats Is Associated With Reduced Blood Pressure

et al. 2013

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“…The combined actions of these transport systems have been extensively reviewed (see e.g. [38, 47, 49, 52, 53]) and are therefore only briefly summarized here. Na + and Cl − are resorbed by entering the cells apically through NKCC2 and leaving the cells basolaterally through the Na + /K + -ATPase and CLC-Kb, respectively.…”

Section: Paracellular Transport In the Talmentioning

confidence: 99%

Function and regulation of claudins in the thick ascending limb of Henle

Günzel

2008

Pflugers Arch - Eur J Physiol

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SUMMARYThe thick ascending limb of Henle mediates transcellular reabsorption of NaCl while generating a lumen-positive voltage that drives passive paracellular reabsorption of divalent cations. Disturbance of paracellular reabsorption leads to Ca 2+ and Mg 2+ wasting in patients with the rare inherited disorder of familial hypercalciuric hypomagnesemia with nephrocalcinosis (FHHNC). Recent work has shown that the claudin family of tight junction proteins form paracellular pores and determine the ion selectivity of paracellular permeability. Importantly, FHHNC has been found to be caused by mutations in two of these genes, claudin-16 and -19, and mice with knockdown of claudin-16 reproduce many of the features of FHHNC. Here, we review the physiology of TAL ion transport, present the current view of the role and mechanism of claudins in determining paracellular permeability, and discuss the possible pathogenic mechanisms responsible for FHHNC.

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“…MR, mineralocorticoid receptor; 11β-HSD, 11β-hydroxysteroid dehydrogenase; ENaC, epithelial Na channel; ROMK, luminal ATP-regulated inwardly rectifying K channel. [From Landau D : Cell Mol Life Sci 63:1962-1968, 2006]…”

Section: Figmentioning

confidence: 99%

“…1). As a result, any condition that decreases the activity of renal potassium channels results in hyperkalemia (for example, amiloride intake or aldosterone deficiency) whereas their increased activity results in hypokalemia (for example, primary aldosteronism or Liddle's syndrome)1, 2). Increased aldosterone, in addition, can cause metabolic alkalosis by increasing bicarbonate reabsorption in the collecting duct.…”

Section: Introductionmentioning

confidence: 99%

Hypertensive Hypokalemic Disorders

Choi

2007

Electrolyte Blood Press

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Hypokalemia is a common clinical problem. The kidney is responsible for long term potassium homoeostasis, as well as the serum potassium concentration. The main nephron site where K secretion is regulated is the cortical collecting duct, mainly via the effects of aldosterone. Aldosterone interacts with the mineralocorticoid receptor to increase sodium reabsorption and potassium secretion; the removal of cationic sodium makes the lumen relatively electronegative, thereby promoting passive potassium secretion from the tubular cell into the lumen through apical potassium channels. As a result, any condition that decreases the activity of renal potassium channels results in hyperkalemia (for example, amiloride intake or aldosterone deficiency) whereas their increased activity results in hypokalemia (for example, primary aldosteronism or Liddle's syndrome). The cause of hypokalemia can usually be determined from the history. If there is no apparent cause, the initial step is to see if hypokalemia is in associated with systemic hypertension or not. In the former group hypokalaemia is associated with a high mineralocorticoid effect or hyperactive sodium channel as in Liddle's syndrome. In hypertensive hypokalemic patients, measurement of the renin, aldosterone, and cortisol concentrations would be of help in differential diagnosis.

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Potassium-related inherited tubulopathies

Cited by 24 publications

References 37 publications

Heterozygous Disruption of Renal Outer Medullary Potassium Channel in Rats Is Associated With Reduced Blood Pressure

Heterozygous Disruption of Renal Outer Medullary Potassium Channel in Rats Is Associated With Reduced Blood Pressure

Function and regulation of claudins in the thick ascending limb of Henle

Hypertensive Hypokalemic Disorders

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