Prostaglandin E2 activates clusters of apical Cl- channels in principal cells via a cyclic adenosine monophosphate-dependent pathway.

Ling, Brian N.; Kokko, Kenneth E.; Eaton, Douglas C.

doi:10.1172/jci117037

Cited by 37 publications

(27 citation statements)

References 38 publications

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“…In addition to these data from intact tubules, there is evidence that CFTRlike Cl-channels are present in the apical membrane of distal nephron cells. Cl -channels with the appropriate single-channel characteristics have been identified in A6 cells (28), primary cultures of rabbit cortical collecting duct (29), and primary cultures of rabbit early distal convoluted tubule (30). We point out that other kinds of Cl-channels have been demonstrated in the apical membrane of distal nephron epithelial cells (28,31).…”

Section: Controlmentioning

confidence: 82%

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Anion secretion by the inner medullary collecting duct. Evidence for involvement of the cystic fibrosis transmembrane conductance regulator.

Husted¹,

Volk²,

Sigmund³

et al. 1995

J. Clin. Invest.

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It is well established that the terminal renal collecting duct is capable of electrogenic Na+ absorption. The present experiments examined other active ion transport processes in primary cultures of the rat inner medullary collecting duct. When the amiloride analogue benzamil inhibited electrogenic Na+ absorption, cAMP agonists stimulated a transmonolayer short circuit current that was not dependent on the presence of Na+ in the apical solution, but was dependent on the presence of Cl -and HCO -. This current was not inhibited by the loop diuretic bumetanide, but was inhibited by ouabain, an inhibitor of the Na+/K+ pump. The current was reduced by anion transport inhibitors, with a profile similar to that seen for inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-channel. Using several PCR strategies, we demonstrated fragments of the predicted lengths and sequence identity with the rat CFTR. Using whole-cell patch-clamp analysis, we demonstrated a cAMP-stimulated Cl -current with characteristics of the CFTR. We conclude that the rat inner medullary collecting duct has the capacity to secrete anions. It is highly likely that the CFTR Cl-channel is involved in this process. (J. Clin. Invest. 1995.95:644-650.)

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Section: Controlmentioning

confidence: 82%

“…The reason that activation of apical membrane Cl-channels could effect either net secretion or absorption is that the electrochemical driving force for Cl-across the apical membrane under "normal" conditions is near 0 (29). The magnitude of the apical membrane voltage is a major determinant of the direction of the net Cl -movement.…”

Section: Controlmentioning

confidence: 99%

Anion secretion by the inner medullary collecting duct. Evidence for involvement of the cystic fibrosis transmembrane conductance regulator.

Husted¹,

Volk²,

Sigmund³

et al. 1995

J. Clin. Invest.

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“…The PKA-stimulated currents have been suggested to be due to CFTR, on the basis of expression of CFTR mRNA and/or protein in these cultured cells, the absence of Cl − currents in cells cultured from CFTR null mice (14), and an anion permeability sequence compatible with CFTR in M1 cells (15). A small apical Cl − conductance has also been found in primary cultures of rabbit principal cells (16,17), and single Cl − channel activity exhibited some of the characteristics of human CFTR. Although these studies suggest that cultured renal principal cells may express CFTR, the presence of CFTR Cl − single-channel activity in native renal tubule epithelial cells and the role of any such channel activity in kidney function have not been established (2).…”

mentioning

confidence: 99%

Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA–regulated apical chloride channels in cortical collecting duct

Lu¹,

Dong²,

Egan

et al. 2010

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

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The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in many segments of the mammalian nephron, where it may interact with and modulate the activity of a variety of apical membrane proteins, including the renal outer medullary potassium (ROMK) K + channel. However, the expression of CFTR in apical cell membranes or its function as a Cl − channel in native renal epithelia has not been demonstrated. Here, we establish that CFTR forms protein kinase A (PKA)-activated Cl − channels in the apical membrane of principal cells from the cortical collecting duct obtained from mice. These Cl − channels were observed in cell-attached apical patches of principal cells after stimulation by forskolin/3-isobutyl-1-methylxanthine. Quiescent Cl − channels were present in patches excised from untreated tubules because they could be activated after exposure to Mg-ATP and the catalytic subunit of PKA. The single-channel conductance, kinetics, and anion selectivity of these Cl − channels were the same as those of recombinant mouse CFTR channels expressed in Xenopus laevis oocytes. The CFTR-specific closed-channel blocker CFTR inh -172 abolished apical Cl − channel activity in excised patches. Moreover, apical Cl − channel activity was completely absent in principal cells from transgenic mice expressing the ΔF508 CFTR mutation but was present and unaltered in ROMK-null mice. We discuss the physiologic implications of open CFTR Cl − channels on salt handling by the collecting duct and on the functional CFTR–ROMK interactions in modulating the metabolic ATP-sensing of ROMK.

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“…Therefore, pH sensitivity is another (but not conclusive) indication that the small-conductance Clchannel discussed here is distinct from the CFTR. Cl-channels having properties similar to those of the CTAL channel have been found in the basolateral membranes of the rabbit proximal tubule (Segal, Geibel & Boulpaep, 1993) and in apical membranes of cultured cells from distal convoluted tubule (Poncet, Tauc, Bidet & Poujeol, 1994) and cortical collecting tubule (Ling, Kokko & Eaton, 1994). There is no evidence that these channels are also sensitive to internal pH.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of a small‐conductance cAMP‐dependent Cl‐ channel in the mouse thick ascending limb at low internal pH.

Guinamard

Paulais

Teulon

1996

The Journal of Physiology

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Prostaglandin E2 activates clusters of apical Cl- channels in principal cells via a cyclic adenosine monophosphate-dependent pathway.

Cited by 37 publications

References 38 publications

Anion secretion by the inner medullary collecting duct. Evidence for involvement of the cystic fibrosis transmembrane conductance regulator.

Anion secretion by the inner medullary collecting duct. Evidence for involvement of the cystic fibrosis transmembrane conductance regulator.

Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA–regulated apical chloride channels in cortical collecting duct

Inhibition of a small‐conductance cAMP‐dependent Cl‐ channel in the mouse thick ascending limb at low internal pH.

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