Amiloride-Sensitive Na+Channels in Human Nasal Epithelium Are Different from Classical Epithelial Na+Channels

Rückes, Claudia; Blank, Ulrike; Möller, Karin; Rieboldt, Jens; Lindemann, H.; Münker, G.; Clauss, Wolfgang; Weber, Wolf-Michael

doi:10.1006/bbrc.1997.7106

Cited by 16 publications

(20 citation statements)

References 10 publications

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“…Yet, to our very surprise we could not spot any of these Cl -conductances by applying the respective blockers the channels are sensitive for. Neither DPC nor DIDS nor NPPB showed any remarkable reduction on I SC in the presence of amiloride, which was applied to circumvent unwanted effects of the Cl -channel blockers on Na + conductances as reported earlier [7]. By comparing the results from non-CF nasal tissue with those obtained from CF nasal cells, we found that there is no difference in Cl -secretion behavior between these 2 groups.…”

Section: Discussionmentioning

confidence: 49%

“…the outwardly rectifying Clchannel (ORCC), had no distinct effect on I SC , demonstrating the lack of DIDS-or DPC-sensitive Cl -conductances in this tissue. Since it has been shown recently that DPC also blocks amiloride-sensitive Na + channel in human nasal epithelium [7], Cl -channel blockers always were applied in the presence of amiloride (100 ÌM). However, we were rather surprised that there also was nearly no remarkable activation of any Cl -conductances in non-CF tissue as demonstrated by the essen-Rückes-Nilges/Weber/Lindemann/ Münker/Clauss/Weber Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Primary cultures of human nasal epithelium have proved to be useful for the study of ion transport defects related to CF [6,7]. These cells can be cultured to form polarized monolayers with quite high transepithelial resistance (R t ), a prerequisite that enables transepithelial electrophysiological approaches.…”

Section: Introductionmentioning

confidence: 99%

“…Using the technique we showed in some recent papers that there is no net balance between Na + absorption and Cl -secretion in primary cultures of human respiratory epithelium and the major part of transepithelial ion transport processes is mediated by Na + in CF as well as in non-CF epithelia [7,8]. In this paper we confirm and extend our previous observations that in human nasal epithelium of CF tissue and, even more surprisingly, non-CF tissue Cl -secretion via CFTR or other Clchannels plays only a minor role in the generation of the total transepithelial short-circuit current.…”

Section: Introductionmentioning

confidence: 99%

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Minor Role of Cl<sup>–</sup> Secretion in Non-Cystic Fibrosis and Cystic Fibrosis Human Nasal Epithelium

Rückes-Nilges¹,

Weber²,

Lindemann³

et al. 1999

Cell Physiol Biochem

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Na⁺ and Cl^– currents were studied in primary cultures of human nasal epithelium derived from non-cystic fibrosis (non-CF) and cystic fibrosis (CF) patients. We found that Na⁺ absorption dominates transepithelial transport and the Na⁺ current contains an amiloride-sensitive and amiloride-insensitive component. In non-CF tissue both components contribute about equally to the entire short-circuit current (I_SC), whereas in CF tissues the major part of the current is amiloride-sensitive. Na⁺ removal reduced I_SC to values close to zero. Several Cl^– channel blockers were used to identify the remaining tiny Na⁺-independent current. Under unstimulated, physiological conditions in the presence of Cl^– on both sides and amiloride on the apical side of the epithelium diphenylamine-2-carboxic acid (DPC), 4,4′-diisothiocyanatostilbene-2,2′- disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) failed to induce clearcut inhibition of I_SC. cAMP as well as ATP did not affect I_SC either in CF or in non-CF epithelia. Reduction of apical Cl^– increased I_SC and depolarized transepithelial potential; however, the observed increase was insensitive to DIDS, DPC and NPPB. From these data we conclude that Cl^– conductances in primary cultures of human nasal epithelium derived from CF patients as well as from non-CF patients are present only in low numbers or do not contribute significantly to transepithelial ion transport.

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Section: Discussionmentioning

confidence: 49%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Minor Role of Cl<sup>–</sup> Secretion in Non-Cystic Fibrosis and Cystic Fibrosis Human Nasal Epithelium

Rückes-Nilges¹,

Weber²,

Lindemann³

et al. 1999

Cell Physiol Biochem

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“…As expected, the control cells had the highest amiloride-sensitive current. It is well known that primary HNE cells have an amiloride-sensitive current [38,39]. In comparison, in cells transfected with different doses of wtCFTR-mRNA the transepithelial ENaC current decreased stepwise, possibly showing a trend in the down-regulation of ENaC by CFTR (Fig.…”

Section: Does the Boosted Cftr Expression Affect Enac?mentioning

confidence: 84%

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

et al. 2016

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Background: Cystic fibrosis (CF) is the most common life-threatening inherited disease in the Caucasian population. It is caused by genetic defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR), a cAMP regulated chloride-bicarbonate channel mainly located in the apical membrane of polarized epithelial cells. CFTR is proposed to regulate other proteins, including the epithelial sodium channel (ENaC). Recently, we successfully restored chloride current in CFTR deficient human airway epithelial cells using wtCFTR-mRNA transfection compared to non-CF cells showing similar values. The present study aimed to optimize the wtCFTR-mRNA transfection procedures in primary cultured human nasal epithelial (HNE) cells. Methods: Dose and time dependence experiments were performed. In addition, we investigated the possible impact of the wtCFTR-mRNA transfection on ENaC function in transepithelial measurements. We reduced the wtCFTR-mRNA dose stepwise and determined the minimal concentration of 0.6 μg/cm

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Specific inhibition of epithelial Na⁺ channels by antisense oligonucleotides for the treatment of Na⁺ hyperabsorption in cystic fibrosis

Sobczak

Segal

Bangel-Ruland

et al. 2009

The Journal of Gene Medicine

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Background Cystic fibrosis (CF) respiratory epithelia are characterized by a defect Cl − secretion and an increased Na + absorption through epithelial Na + channels (ENaC). The present study aimed to find an effective inhibitor of human ENaC with respect to replacing amiloride therapy for CF patients. Therefore, we developed specific antisense oligonucleotides (AON) that efficiently suppress Na + hyperabsorption by inhibiting the expression of the α-ENaC subunit.

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Amiloride-Sensitive Na+Channels in Human Nasal Epithelium Are Different from Classical Epithelial Na+Channels

Cited by 16 publications

References 10 publications

Minor Role of Cl<sup>–</sup> Secretion in Non-Cystic Fibrosis and Cystic Fibrosis Human Nasal Epithelium

Minor Role of Cl<sup>–</sup> Secretion in Non-Cystic Fibrosis and Cystic Fibrosis Human Nasal Epithelium

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

Specific inhibition of epithelial Na⁺ channels by antisense oligonucleotides for the treatment of Na⁺ hyperabsorption in cystic fibrosis

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Amiloride-Sensitive Na+Channels in Human Nasal Epithelium Are Different from Classical Epithelial Na+Channels

Cited by 16 publications

References 10 publications

Minor Role of Cl<sup>–</sup> Secretion in Non-Cystic Fibrosis and Cystic Fibrosis Human Nasal Epithelium

Minor Role of Cl<sup>–</sup> Secretion in Non-Cystic Fibrosis and Cystic Fibrosis Human Nasal Epithelium

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

Specific inhibition of epithelial Na+ channels by antisense oligonucleotides for the treatment of Na+ hyperabsorption in cystic fibrosis

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Specific inhibition of epithelial Na⁺ channels by antisense oligonucleotides for the treatment of Na⁺ hyperabsorption in cystic fibrosis