Arachidonic acid inhibits activity of cloned renal K+ channel, ROMK1

Macica, Carolyn M.; Yang, Yanmin; Hebert, S. C.; Wang, Wen Hui

doi:10.1152/ajprenal.1996.271.3.f588

Cited by 41 publications

(37 citation statements)

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“…Xenopus laevis females were obtained from NASCO (Fort Atkinson, WI). The method for obtaining oocytes has been described previously (33). Viable oocytes were selected for injection with different cRNA.…”

Section: Methodsmentioning

confidence: 99%

Inhibitor of growth 4 (ING4) is up-regulated by a low K intake and suppresses renal outer medullary K channels (ROMK) by MAPK stimulation

Zhang

Lin

Jin

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Dietary K intake plays an important role in the regulation of renal K secretion: a high K intake stimulates whereas low K intake suppresses renal K secretion. Our previous studies demonstrated that the Src family protein-tyrosine kinase and mitogen-activated protein kinase (MAPK) are involved in mediating the effect of low K intake on renal K channels and K secretion. However, the molecular mechanism by which low K intake stimulates MAPK is not completely understood. Here we show that inhibitor of growth 4 (ING4), a protein with a highly conserved plant homeodomain finger motif, is involved in mediating the effect of low K intake on MAPK. K restriction stimulates the expression of ING4 in the kidney and superoxide anions, and its related products are involved in mediating the effect of low K intake on ING4 expression. We used HEK293 cells to express ING4 and observed that expression of ING4 increased the phosphorylation of p38 and ERK MAPK, whereas down-regulation of ING4 with small interfering RNA decreased the phosphorylation of p38 and ERK. Immunocytochemistry showed that ING4 was expressed in the renal outer medullary potassium (ROMK)-positive tubules. Moreover, ING4 decreased K currents in Xenopus oocytes injected with ROMK channel cRNA. This inhibitory effect was reversed by blocking p38 and ERK MAPK. These data provide evidence for the role of ING4 in mediating the effect of low K intake on ROMK channel activity by stimulation of p38 and ERK MAPK.ERK ͉ hypokalemia ͉ p38 ͉ renal potassium metabolism ͉ superoxide I t is well known that low K intake suppresses renal K secretion by increasing K absorption and inhibiting K secretion (1, 2). The inhibitory effect of low K intake on renal K secretion is partially achieved by removing renal outer medullary potassium (ROMK)-like small conductance K channels from the apical membrane of principal cells in the cortical collecting duct (CCD) through a protein-tyrosine kinase (PTK)-dependent mechanism (3). We have demonstrated previously that low K intake stimulates the production of superoxide anions and its related products, which in turn increase PTK expression and activity (4, 5). Increased PTK activity stimulates tyrosine phosphorylation of ROMK channels and subsequently enhances the internalization of the ROMK channels (6, 7). Furthermore, we have shown that low K intake stimulates ERK and p38 MAPK, which inhibits ROMK channels by a PTKindependent pathway. However, the mechanism by which low K intake stimulates MAPK activity is not completely understood.Inhibitor of growth 4 (ING4) is a member of the ING family proteins. They have been shown to regulate cell cycle, transcription and oncogenesis (8), and to promote UV-induced apoptosis of skin cells (9). ING4 also plays an important role in inhibiting tumor growth and angiogenesis in brain tumor cells (10). Because K restriction causes renal hypertrophy (11) through stimulation of growth factor levels (12), it is possible that that ING family proteins may also be involved in mediating the effect of low K intake on...

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Section: Methodsmentioning

confidence: 99%

Inhibitor of growth 4 (ING4) is up-regulated by a low K intake and suppresses renal outer medullary K channels (ROMK) by MAPK stimulation

Zhang

Lin

Jin

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…13 The inhibitory action on the NKCC cotransporter is possibly mediated by impaired apical K ϩ -channel recycling of K ϩ . 14 Dahl salt-sensitive (SS) rats exhibit a deficit in outer renal medullary synthesis of 20-HETE, which has been implicated in their increased thick ascending limb chloride transport, shifted pressure-natriuresis, and salt-dependent hypertension. 15 In humans, we have shown that the relationship between urine excretion of 20-HETE and sodium differs between SS and salt-resistant (SR) hypertensive patients, suggesting a role for this eicosanoid in determining saltsensitivity of blood pressure (BP).…”

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confidence: 99%

20-HETE and Furosemide-Induced Natriuresis in Salt-Sensitive Essential Hypertension

et al. 2003

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Abstract-Cyclooxygenase metabolites of arachidonic acid modulate the natriuretic effect of furosemide. It is not known whether 20-HETE, a monooxygenase metabolite of arachidonic acid that also inhibits sodium transport, participates in the action of furosemide. We measured urine sodium (UNaV) and 20-HETE during furosemide diuresis (40 mg three times over 12 hours) in 12 salt-sensitive (SS) and 11 salt-resistant (SR), salt-replete hypertensive subjects (126Ϯ24 mmol/24 hours positive sodium balance produced by 160-mmol-sodium diet and 2 L saline infusion). Individual systolic blood pressure decreases from the salt-replete to the salt-depleted state were the index of salt-sensitivity. SS had low plasma renin with blunted responses to changes in salt balance, inappropriate plasma aldosterone, and an increased aldosterone/renin ratio.

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“…The OMCD cells appear to express only the ROMK1 transcript (9). The general single channel properties (measured from the oocyte expression with single channel recording) of ROMK1, -2, and -3 isoforms are similar (20,21). However, the specific functional and regulation consequences of the different ROMK isoforms have not been fully elucidated in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…The unique structural difference between ROMK1 and ROMK2 is that ROMK1 extended N-terminal with specific binding sites of hormones and protein kinase. For example, the ROMK1 channel is sensitive to arachidonic acid (20,21), but arachidonic acid has little to no effect on ROMK2 and ROMK3 (20). ROMK1 channel activity could also be regulated by monoubiquitination, and the ubiquitin binding site is on lysine 22 on the N terminus of ROMK1 (12).…”

Section: Discussionmentioning

confidence: 99%

Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion

Dong

Yan

et al. 2016

Journal of Biological Chemistry

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Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell CreLoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. The renal outer medullary potassium channel (ROMK) 3 is an ATP-dependent potassium channel (Kir1.1) that forms apical K channels that play an important role in K ϩ recycling to support sodium and chloride absorption in the thick ascending limb (TAL), and in regulation of K ϩ secretion in the collecting duct (CD). Mutations in the ROMK channel cause Type II Bartter syndrome that presents with polyhydramnios and postnatal life threatening volume depletion caused by loss of salt reabsorbing capacity by the thick ascending limb (1). Romk knock-out mice, originally generated from Gary Shull's lab at the University of Cincinnati, exhibited the same phenotypes as the Bartter syndrome in humans (2). By using the Romk Bartter mouse model, we have further confirmed that ROMK forms both small conductance K ϩ channels (SK) and 70 pS K channels in apical membranes of the thick ascending limb and cortical collecting duct (3, 4). We have demonstrated: 1) absence of both SK activity and 70 pS K ϩ channels in apical membranes of thick ascending limb and cortical collecting duct in Romk knock-out mice; 2) Romk knock-out mice produced similar phenotypes to Bartter syndrome consisting of salt and water wasting due to reduced NKCC2 activity and expression (3, 5); 3) the salt and water wasting from the kidney is compensated by increased thiazide-sensitive NaCl transport expression and activity, distal tubule hypertrophy, elevated renin-Ang II, and aldosterone levels (6). 4) The reduced K ϩ secretion in Romk null mice is compensated by increased maxi-K channel activity in the collecting tubule (7).However, three ROMK isoforms (ROMK1, -2, and -3) have been identified in the rat kidney (8 -10), but unique functions of any of the ROMK isoforms in nephron segments are still poorly understood. ROMK1 is expressed in the distal and collecting tubules and uniquely regulated by PTK/PTP-dependent endocytosis, which may be the mechanism for high-K-mediated enhanced ROMK channel activity in the collecting tubule (11,12). To study the functional role of ROMK1 in the regulation of Na and K homeostasis, we have generated a mouse deficient only in Romk1 by selective deletion of the Romk1 exon, using an ES cell Cre-LoxP strategy. We have examined the phenotypes of these mice by metabolic and renal clearance, and examined K channel activities by the patch clamp. The ion transporters, Nkcc2, Ncc, and Romk2, expression were measured by Q-PCR and ROMK localization was examined by immun...

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Arachidonic acid inhibits activity of cloned renal K+ channel, ROMK1

Cited by 41 publications

References 0 publications

Inhibitor of growth 4 (ING4) is up-regulated by a low K intake and suppresses renal outer medullary K channels (ROMK) by MAPK stimulation

Inhibitor of growth 4 (ING4) is up-regulated by a low K intake and suppresses renal outer medullary K channels (ROMK) by MAPK stimulation

20-HETE and Furosemide-Induced Natriuresis in Salt-Sensitive Essential Hypertension

Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion

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