K Depletion Enhances the Extracellular Ca2+-Induced Inhibition of the Apical K Channels in the Mtal of Rat Kidney

Gu, Ruimin; Wei, Yuan; Jiang, Ho-Lin; Lin, Dao‐Hong; Sterling, Hyacinth; Bloom, Peter; Balazy, Micheal; Wang, Wenhui

doi:10.1085/jgp.119.1.33

Cited by 16 publications

(8 citation statements)

References 36 publications

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“…In addition to the larger single-channel conductance, several factors may be involved in the specific activation of the 70-pS K channel by a high dietary K intake. 20-Hydroxyeicosatetraenic acid (20-HETE) is a potent inhibitor of the 70-pS K channel, and 20-HETE production has been shown to be lower in TAL cells from rats placed on a high-K diet (8). Furthermore, inhibition of 20-HETE production by cytochrome P-450 increases 70-pS K channel activity (6).…”

Section: Discussionmentioning

confidence: 99%

ROMK is required for expression of the 70-pS K channel in the thick ascending limb

Wang²,

Yan³

et al. 2004

American Journal of Physiology-Renal Physiology

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Apical potassium recycling is crucial for salt transport by the thick ascending limb (TAL). Loss-of-function mutations in the K channel, ROMK (Kir1.1; KCNJ1), cause Bartter syndrome, a genetically heterogeneous disorder characterized by severe reduction in salt absorption by the TAL, Na wasting, polyuria, and hypokalemic alkalosis. ROMK(-/-) null mice exhibit a Bartter phenotype and lack the small-conductance (30-pS) apical K channel (SK) in the TAL. However, a distinct 70-pS K channel can also significantly contribute to the apical conductance of TAL. We now examine the effect of ROMK deletion on the functional expression of the 70-pS K channel in the TAL. Functional expression of the 70-pS K channel was low [average channel activity (NP(o)) = 0.02] in ROMK(+/+) mice on a control K diet but increased to 0.27 by high-K intake for 2 wk. In contrast, the high-K diet decreased NP(o) of SK by approximately 30%, from 2.04 to 1.44. In ROMK heterozygous (+/-) mice on a control K diet, SK activity was about one-half of that observed in ROMK(+/+) mice (0.95 vs. 2.04). The high-K diet also reduced SK activity in ROMK(+/-) mice by approximately 40% (from 0.95 to 0.55) but increased NP(o) of the 70-pS K channel from 0 to 0.09 in ROMK(+/-) mice. This corresponds to approximately 30% of channel activity (NP(o) = 0.27) observed in ROMK(+/+) mice. Neither the 70-pS nor the 30-pS K channels were observed in TAL cells from ROMK(-/-) mice on either the normal or high-K diets. Thus functional expression of the 70-pS K channel is enhanced by increasing dietary K and requires expression of ROMK. It is likely that ROMK forms a critical subunit of the 70-pS K channel, accounting for the loss of apical K secretory channel activity in ROMK Bartter syndrome.

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Section: Discussionmentioning

confidence: 99%

ROMK is required for expression of the 70-pS K channel in the thick ascending limb

Wang²,

Yan³

et al. 2004

American Journal of Physiology-Renal Physiology

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“…However, mTAL is very easy to recognize because the size of the mTAL is larger than that of thin descending limb but smaller than that of collecting duct. Moreover, we have carried out a large amount of experiments studying the apical ROMK and 70 pS K channels, which is expressed uniquely in the TAL 49. Thus, we are very familiar with the morphological characteristic of the mTAL.…”

Section: Methodsmentioning

confidence: 99%

CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10pS chloride channel in the rat thick ascending limb

Liu

Zhang

et al. 2009

Kidney International

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Metabolites of arachidonic acid influence sodium chloride (NaCl) transport in the thick ascending limb. Because a 10 pS Cl channel is the major type of chloride channel in the basolateral membrane of this nephron segment, we explored the effect of arachidonic acid on this channel in cell-attached patches. Addition of 5μmol arachidonic acid significantly decreased channel activity (a product of channel number and open probability) while linoleic acid had no effect. To determine if this was mediated by acachidonic acid per se or by its metabolites, we measured channel activity in the presence of the cyclooxygenase inhibitor indomethacin, the selective lipoxygenase inhibitor nordihydroguaiaretic acid, and the cytochrome P-450 (CYP)-ω-hydroxylation inhibitor 17-octadecynoic acid. Neither cyclooxygenase nor lipoxygenase inhibition had an effect on basal chloride channel activity; further they failed to abolish the inhibitory effect of arachidonate on the 10 pS channel. However, inhibition of CYP-ω-hydroxylation completely abolished the effect of arachidonic acid. The similarity of the effects of 20-hydroxyeicosatetraenoic acid (20-HETE) and arachidonic acid suggests that the effect of arachidonic acid was mediated by CYP-ω-hydroxylation-dependent metabolites. We conclude that arachidonic acid inhibits the 10 pS chloride channel in the basolateral membrane of the medullary thick ascending limb, an effect mediated by the CYP-ω-hydroxylation-dependent metabolite 20-HETE.

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“…Although we can postulate that a gut factor, glucagon, and uroguanylin are mediators, there is scant evidence that can explain regulation at the level of receptors and transporters. At the subcellular level, signaling studies in the thick ascending limb, a region in which Na + and volume reabsorption is inhibited during high K + intake, show that a high-K + diet is associated with increases in both inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production as well as heme oxygenase 2 and carbon monoxide (CO) production (58, 59). Both NO, via cGMP, and CO stimulate the 70-pS ROMK-related channel in the thick ascending limb apical membrane.…”

Section: Molecular Mechanisms Of Renal K+ Adaptationmentioning

confidence: 99%

Recent Advances in Understanding Integrative Control of Potassium Homeostasis

Youn

McDonough

2009

Annu. Rev. Physiol.

118

108

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The potassium homeostatic system is very tightly regulated. Recent studies have shed light on the sensing and molecular mechanisms responsible for this tight control. In addition to classic feedback regulation mediated by a rise in extracellular fluid (ECF) [K+], there is evidence for a feedforward mechanism: Dietary K+ intake is sensed in the gut, and an unidentified gut factor is activated to stimulate renal K+ excretion. This pathway may explain renal and extrarenal responses to altered K+ intake that occur independently of changes in ECF [K+]. Mechanisms for conserving ECF K+ during fasting or K+ deprivation have been described: Kidney NADPH oxidase activation initiates a cascade that provokes the retraction of K+ channels from the cell membrane, and muscle becomes resistant to insulin stimulation of cellular K+ uptake. How these mechanisms are triggered by K+ deprivation remains unclear. Cellular AMP kinase–dependent protein kinase activity provokes the acute transfer of K+ from the ECF to the ICF, which may be important in exercise or ischemia. These recent advances may shed light on the beneficial effects of a high-K+ diet for the cardiovascular system.

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K Depletion Enhances the Extracellular Ca2+-Induced Inhibition of the Apical K Channels in the Mtal of Rat Kidney

Cited by 16 publications

References 36 publications

ROMK is required for expression of the 70-pS K channel in the thick ascending limb

ROMK is required for expression of the 70-pS K channel in the thick ascending limb

CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10pS chloride channel in the rat thick ascending limb

Recent Advances in Understanding Integrative Control of Potassium Homeostasis

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