Control of NaCl transport in the thick ascending limb

Hebert, Steven C.; Andreoli, Thomas E.

doi:10.1152/ajprenal.1984.246.6.f745

Cited by 174 publications

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“…The mTAL is responsible for the reabsorption of 25% of filtered Na load and plays a key role in mediating urinary concentrating ability (10,11,16). Na and Cl enter the cell across the apical membrane through the Na-K-2Cl cotransporters, and Na is then actively transported across the basolateral membrane by Na-K-ATPase, whereas Cl leaves the cell via KCl cotransporters or Cl channels (10,11).…”

Section: Discussionmentioning

confidence: 99%

“…1), which partially determines the Cl diffusion potential across the basolateral membrane (26). Cl ions enter the cell across the apical membrane via Na-K-2Cl cotransporters and leave the cell across the basolateral membrane through KCl cotransporters or Cl channels along its electrochemical gradient (10,11,16). The driving force for the Cl exit across the basolateral membrane is the Cl electrochemical gradient, which is the difference between the chemical gradient of Cl and the cell membrane potential.…”

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Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Wang

2002

American Journal of Physiology-Renal Physiology

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We have used the patch-clamp technique to study the effect of arachidonic acid (AA) on the basolateral K channels in the medullary thick ascending limb (mTAL) of rat kidney. An inwardly rectifying 50-pS K channel was identified in cell-attached and inside-out patches in the basolateral membrane of the mTAL. The channel open probability (Po) was 0.51 at the spontaneous cell membrane potential and decreased to 0.25 by 30 mV hyperpolarization. The addition of 5 M AA decreased channel activity, identified as NPo, from 0.58 to 0.08 in cell-attached patches. The effect of AA on the 50-pS K channel was specific because 10 M cis-11,14,17-eicosatrienoic acid had no significant effect on channel activity. To determine whether the effect of AA was mediated by AA per se or by its metabolites, we examined the effect of AA on channel activity in the presence of indomethacin, an inhibitor of cyclooxygenase, or N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), an inhibitor of cytochrome P-450 monooxygenase. Inhibition of cyclooxygenase increased channel activity from 0.54 to 0.9. However, indomethacin did not abolish the inhibitory effect of AA on the 50-pS K channel. In contrast, inhibition of cytochrome P-450 metabolism not only increased channel activity from 0.49 to 0.83 but also completely abolished the effect of AA. Moreover, addition of DDMS can reverse the inhibitory effect of AA on channel activity. The notion that the effect of AA was mediated by cytochrome P-450-dependent metabolites of AA is also supported by the observation that addition of 100 nM of 20-hydroxyeicosatetraenoic acid, a main metabolite of AA in the mTAL, can mimic the effect of AA. We conclude that AA inhibits the 50-pS K channel in the basolateral membrane of the mTAL and that the effect of AA is mainly mediated by cytochrome P-450-dependent metabolites of AA.cyclooxygenase; cytochrome P-450 -oxidation; 20-hydroxyeicosatetraenoic acid; basolateral K channel K CHANNELS IN THE BASOLATERAL membrane of the medullary thick ascending limb (mTAL) play an important role in the regulation of epithelial transport in the loop of Henle. The basolateral K channels in the mTAL are responsible for K recycling across the basolateral membrane and participate in generating the cell membrane potential (Fig.

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Section: Discussionmentioning

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Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Wang

2002

American Journal of Physiology-Renal Physiology

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“…This lumen-positive potential difference plays a critical role in physiology of the TAL, driving the paracellular transport of Na 1 , Ca 21 , and Mg 21 (see Figure 2). The conductivity of the apical membrane of TAL cells is predominantly K 1 selective; luminal recycling of K 1 via Na 1 -K 1 -2Cl 2 cotransport and apical K 1 channels, along with basolateral depolarization due to Cl 2 exit through Cl 2 channels, generates the lumen-positive transepithelial potential difference (19,20).…”

Section: Anatomy and Morphologymentioning

confidence: 99%

Thick Ascending Limb of the Loop of Henle

Mount

2014

Clinical Journal of the American Society of Nephrology

139

106

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The thick ascending limb occupies a central anatomic and functional position in human renal physiology, with critical roles in the defense of the extracellular fluid volume, the urinary concentrating mechanism, calcium and magnesium homeostasis, bicarbonate and ammonium homeostasis, and urinary protein composition. The last decade has witnessed tremendous progress in the understanding of the molecular physiology and pathophysiology of this nephron segment. These advances are the subject of this review, with emphasis on particularly recent developments.

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“…4 Greater Na reabsorption in blacks appeared to take place at a more proximal nephron site. The thick ascending limb (TAL), a principal nephron region for reclamation of Na by way of the Na,K,2Cl cotransporter (NKCC2), 5 is a potential site for increased Na reabsorption. Although NKCC2 in TAL is more active in the salt-sensitive hypertensive Dahl rat, 6,7 NKCC2 has never been shown to cause hypertension in humans.…”

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Ethnic Differences in Renal Responses to Furosemide

et al. 2008

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Abstract-Blacks have a greater tendency to retain Na than whites. The present study sought evidence for ethnic differences in parameters reflective of Na uptake by the Na,K,2Cl cotransporter in the thick ascending limb, namely, the urine concentration and urinary excretion of certain cations before and after furosemide administration (40 mg IV). Subjects were healthy (ages 18 to 36 years). During the preceding overnight period, urine volume was lower, and osmolality was higher in blacks than in whites, an ethnic difference that disappeared when water intake was restricted to infused normal saline (60 mL/h). Plasma vasopressin levels were higher in black males than in other sex/ethnic groups. Baseline urinary excretion rates of K, Ca, and Mg were significantly lower in blacks than in whites. After furosemide (0 to 1 hour), K and Ca excretion rates increased, but the proportionate ethnic difference decreased from 44% to 22% and from 22% to 10%, respectively, consistent with blacks having more basal Na,K,2Cl cotransporter activity to inhibit. During a later postfurosemide period (1 to 5 hours), urinary concentrations of Ca and Mg recovered more slowly in blacks, consistent with greater reuptake in the thick ascending limb. In summary, there were distinct ethnic differences in renal handling of Ca and Mg basally and in response to furosemide that were consistent with a more active Na,K,2Cl cotransporter in the thick ascending limb in blacks. An increase in vasopressin levels appeared to explain greater urine concentrations in black males but not black females. Key Words: Na,K,2Cl cotransporter Ⅲ aldosterone Ⅲ thick ascending limb Ⅲ osmolality Ⅲ ethnicity Ⅲ furosemide Ⅲ calcium B lacks, in comparison with whites, have lower levels of plasma renin activity (PRA) 1 and aldosterone 2 and are more likely to develop hypertension that is salt sensitive, 3 findings consistent with blacks having greater renal reabsorption of Na. Where in the nephron the greater uptake of Na occurs is unknown. We showed previously that amiloride, an inhibitor of the epithelial Na channel in distal nephron, significantly lowered blood pressure in whites when compared with blacks, consistent with less Na uptake by the epithelial Na channel in blacks, probably because of lower aldosterone levels. 4 Greater Na reabsorption in blacks appeared to take place at a more proximal nephron site. The thick ascending limb (TAL), a principal nephron region for reclamation of Na by way of the Na,K,2Cl cotransporter (NKCC2), 5 is a potential site for increased Na reabsorption. Although NKCC2 in TAL is more active in the salt-sensitive hypertensive Dahl rat, 6,7 NKCC2 has never been shown to cause hypertension in humans.Ethnic differences suggesting that TAL could be a site for more active Na uptake in blacks are described here: (1) Blacks have, on average, lower urine volumes and higher urine concentrations than whites. 8,9 Na taken up by NKCC2 in TAL is essential for maintaining the renal medullary osmotic gradient required for water reabsorption in the coll...

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Control of NaCl transport in the thick ascending limb

Cited by 174 publications

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Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Thick Ascending Limb of the Loop of Henle

Ethnic Differences in Renal Responses to Furosemide

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