Phospholipase A2 is involved in mediating the effect of extracellular Ca2+ on apical K+ channels in rat TAL

Wang, W.; Lu, Ming; Balazy, Michael; Hebert, S. C.

doi:10.1152/ajprenal.1997.273.3.f421

Cited by 82 publications

(76 citation statements)

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“…Results summarized in Fig. 9 show that treatment of mTAL cells with 10 nM TNF increased the release of 32 P from the substrate from 2,050 Ϯ 100 pmol/mg protein (control) to 4,200 Ϯ 300 pmol/mg protein (n ϭ 4). The effect of TNF on PTP was specific because TNF did not alter the activity of PTK (control 35,777 Ϯ 2,000 pmol/mg protein, TNF 35,250 Ϯ 2,100 pmol/mg protein, n ϭ 5) in mTAL cells.…”

Section: Resultsmentioning

confidence: 95%

“…In addition, it is possible that ROMK is an important component of both 70-and 30-pS K ϩ channels because neither K ϩ channel can be found in ROMK knockout mice (18). We showed that apical K channels are regulated by a variety of signaling pathways, including nitric oxide (NO), protein kinase C, and protein tyrosine phospatase (PTP) (12,19,32). TNF has been shown to activate these same pathways (1,5,16,20,35).…”

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confidence: 99%

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Acute application of TNF stimulates apical 70-pS K⁺channels in the thick ascending limb of rat kidney

Wei

Babilonia

Pedraza

et al. 2003

American Journal of Physiology-Renal Physiology

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. Acute application of TNF stimulates apical 70-pS K ϩ channels in the thick ascending limb of rat kidney. Am J Physiol Renal Physiol 285: F491-F497, 2003; 10.1152 10. /ajprenal.00104.2003 has been shown to be synthesized by the medullary thick ascending limb (mTAL) (21). In the present study, we used the patch-clamp technique to study the acute effect of TNF on the apical 70-pS K ϩ channel in the mTAL. Addition of TNF (10 nM) significantly stimulated activity of the 70-pS K ϩ channel and increased NPo [a product of channel open probability (Po) and channel number (N)] from 0.20 to 0.97. The stimulatory effect of TNF was observed only in cell-attached patches but not in excised patches. Moreover, addition of TNF had no effect on the ROMK-like small-conductance K ϩ channels in the TAL. The dose-response curve of the TNF effect yielded a Km value of 1 nM, a concentration that increased channel activity to 50% maximal stimulatory effect of TNF. The concentrations required for reaching the plateau of the TNF effect were between 5 and 10 nM. The stimulatory effect of TNF on the 70-pS K ϩ channel was observed in the presence of N -nitro-L-arginine methyl ester. This indicated that the effect of TNF was not mediated by a nitric oxidedependent pathway. Also, inhibition of PKA did not affect the stimulatory effect of TNF. In contrast, inhibition of protein tyrosine kinase not only increased activity of the 70-pS K ϩ channel but also abolished the effect of TNF. Moreover, inhibition of protein tyrosine phosphatase (PTP) blocked the stimulatory effect of TNF on the 70-pS K ϩ channel. The notion that the TNF effect results from stimulation of PTP activity is supported by PTP activity assay in which treatment of mTAL cells with TNF significantly increased the activity of PTP. We conclude that TNF stimulates the 70-pS K ϩ channel via stimulation of PTP in the mTAL.

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Section: Resultsmentioning

confidence: 95%

mentioning

confidence: 99%

Acute application of TNF stimulates apical 70-pS K⁺channels in the thick ascending limb of rat kidney

Wei

Babilonia

Pedraza

et al. 2003

American Journal of Physiology-Renal Physiology

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“…In rat isolated TAL, it has been shown by using the patch-clamp technique and fluorescence dyes that the CaSR activation induces a reduction in the activity of the apical intermediate conductance K ϩ channel and a decrease in intracellular Na ϩ , suggesting inhibition of Na ϩ transport (33). Nevertheless, the K ϩ channel involved in antenatal Bartter syndrome, ROMK, is a low-conductance channel, and its inhibition by activation of CaSR has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of a Calcium-Sensing Receptor Mutation in Severe Autosomal Dominant Hypocalcemia with a Bartter-Like Syndrome

Vargas‐Poussou¹,

Huang²,

Hulin³

et al. 2002

Journal of the American Society of Nephrology

310

195

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Abstract. The extracellular Ca 2ϩ -sensing receptor (CaSR) plays an essential role in extracellular Ca 2ϩ homeostasis by regulating the rate of parathyroid hormone (PTH) secretion and the rate of calcium reabsorption by the kidney. Activation of the renal CaSR is thought to inhibit paracellular divalent cation reabsorption in the cortical ascending limb (cTAL) both directly and indirectly via a decrease in NaCl transport. However, in patients with autosomal dominant hypocalcemia (ADH), caused by CaSR gain-of-function mutations, a defect in tubular NaCl reabsorption with renal loss of NaCl has not been described so far. This article describes a patient with ADH due to a gain-of-function mutation in the CaSR, L125P, associated with a Bartter-like syndrome that is characterized by a decrease in distal tubular fractional chloride reabsorption rate and negative NaCl balance with secondary hyperaldosteronism and hypokalemia. The kinetics of activation of the L125P mutant receptor expressed in HEK-293 cells, assessed by measuring CaSR-stimulated changes in intracellular Ca 2ϩ and ERK activity, showed a dramatic reduction in the EC 50 for extracellular Ca 2ϩ compared with the wild-type and a loss-offunction mutant CaSR (I40F). This study describes the first case of ADH associated with a Bartter-like syndrome. It is herein proposed that the L125P mutation of the CaSR, which represents the most potent gain-of-function mutation reported so far, may reduce NaCl reabsorption in the cTAL sufficiently to result in renal loss of NaCl with secondary hyperaldosteronism and hypokalemia.

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“…Stimulation of the Ca 2ϩ -sensing receptor has been shown to increase 20-HETE production (28). Because the Ca 2ϩ -sensing receptor is located in the basolateral membrane of the mTAL, it is conceivable that the stimulation of the Ca 2ϩ -sensing receptor may also inhibit the basolateral 50-pS K channel.…”

Section: Discussionmentioning

confidence: 99%

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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Phospholipase A2 is involved in mediating the effect of extracellular Ca2+ on apical K+ channels in rat TAL

Cited by 82 publications

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Acute application of TNF stimulates apical 70-pS K⁺channels in the thick ascending limb of rat kidney

Acute application of TNF stimulates apical 70-pS K⁺channels in the thick ascending limb of rat kidney

Functional Characterization of a Calcium-Sensing Receptor Mutation in Severe Autosomal Dominant Hypocalcemia with a Bartter-Like Syndrome

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

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Phospholipase A2 is involved in mediating the effect of extracellular Ca2+ on apical K+ channels in rat TAL

Cited by 82 publications

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Acute application of TNF stimulates apical 70-pS K+channels in the thick ascending limb of rat kidney

Acute application of TNF stimulates apical 70-pS K+channels in the thick ascending limb of rat kidney

Functional Characterization of a Calcium-Sensing Receptor Mutation in Severe Autosomal Dominant Hypocalcemia with a Bartter-Like Syndrome

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

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Acute application of TNF stimulates apical 70-pS K⁺channels in the thick ascending limb of rat kidney

Acute application of TNF stimulates apical 70-pS K⁺channels in the thick ascending limb of rat kidney