Liquid and Ion Transport by Fetal Airway and Lung Epithelia of Mice Deficient in Sodium-Potassium-2-Chloride Transporter

Gillie, Daniel J.; Pace, Amy J.; Coakley, Ray J.; Koller, Beverly H.; Barker, Pierre

doi:10.1165/ajrcmb.25.1.4500

Cited by 37 publications

(34 citation statements)

References 40 publications

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“…In that study, Grubb and colleagues demonstrated that loop diuretics neither affected Cl Ϫ secretion under basal conditions, nor during forskolin-induced Cl Ϫ secretion. A minor role for the NKCC in pulmonary ion transport can also be deduced from reports that NKCC knockout animals develop normal lungs and do not exhibit obvious abnormalities concerning pulmonary ion transport properties and Cl Ϫ secretion, in particular (15). Interestingly, the present study observed a loop diureticsensitive current by establishing a Cl Ϫ gradient as achieved using apical Cl Ϫ -free solution.…”

Section: -Test)supporting

confidence: 73%

“…AE activity was observed in various airway epithelia (11), as well as in alveolar type II pneumocytes (23). Further significance concerning the importance of HCO 3 Ϫ /Cl Ϫ exchanger in pulmonary Cl Ϫ transport is provided by studies using NKCC knockout mice (15). That study concluded that normal lung development in these animals might be due to the function of basolateral HCO 3 Ϫ /Cl Ϫ exchangers bypassing the loss of NKCC function.…”

Section: -Test)mentioning

confidence: 98%

“…Application of the common Cl Ϫ channel blocker NPPB (100 M, apical side) led to a decrease in ISC in accordance with inhibition of apical Cl Ϫ secretion. The effect of NPPB was more pronounced when chlorzoxazone was applied prior to NPPB (*P Ͻ 0.05; (15,26,40). To evaluate the function of this, exchanger experiments with DIDS, a common blocker of the HCO 3 Ϫ /Cl Ϫ anion exchanger (15), were performed (Fig.…”

Section: -Test) E: Inhibition Of CLmentioning

confidence: 99%

“…This assumption was further supported by experiments using acetazolamide perfusion prior to DIDS application. Acetazolamide is a known inhibitor of carbonic anhydrase (15). Carbonic anhydrase is responsible for the production of HCO 3 Ϫ , the intracellular substrate for the HCO 3 …”

Section: /Clmentioning

confidence: 99%

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Basolateral Cl⁻uptake mechanisms in Xenopus laevis lung epithelium

Berger

Hardt

Clauss

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Section: -Test)supporting

confidence: 73%

Section: -Test)mentioning

confidence: 98%

Section: -Test) E: Inhibition Of CLmentioning

confidence: 99%

Section: /Clmentioning

confidence: 99%

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Basolateral Cl⁻uptake mechanisms in Xenopus laevis lung epithelium

Berger

Hardt

Clauss

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The Cl − channels may participate in fluid secretion in fetal lungs since the lung undergoes a change from fluid secretion to absorption at birth. However, CFTR and NKCC knock-out mice were not fatal (Gillie et al, 2001;Snouwaert et al, 1992). In these mice, other Cl − channels may compensate for those channels.…”

Section: Significancementioning

confidence: 98%

Ionotropic GABA receptor expression in the lung during development

Jin

Guo

Sun

et al. 2008

Gene Expression Patterns

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Cl − transport is essential for lung development. Because gamma-aminobutyric acid (GABA) receptors allow the flow of negatively-charged Cl − ions across the cell membrane, we hypothesized that the expression of ionotropic GABA receptors are regulated in the lungs during development. We identified 17 GABA receptor subunits in the lungs by real-time PCR. These subunits were categorized into 4 groups: Group 1 had high mRNA expression during fetal stages and low in adults; Group 2 had steady expression to adult stages with a slight up-regulation at birth; Group 3 showed an increasing expression from fetal to adult lungs; and Group 4 displayed irregular mRNA fluctuations. The protein levels of selected subunits were also determined by Western blots and some subunits had protein levels that corresponded to mRNA levels. Further studied subunits were primarily localized in epithelial cells in the developing lung with differential mRNA expression between isolated cells and whole lung tissues. Our results add to the knowledge of GABA receptor expression in the lung during development. Keywordslungs; ionotropic GABA receptor; fetal lung development; chloride homeostasis; lung fluid transport; real time PCR; gene expression; alveolar epithelial cells RESULTS AND DISCUSSION SignificanceCl − channels play an important role in the lung throughout an animal's life. During the fetal stages, the lung is a fluid-secreting organ. The main driving force for fluid secretion is the active secretion of Cl − into the developing lungs. Therefore, Cl − channels are indispensable for fetal lung development and morphogenesis (Folkesson et al., 1998;Olver et al., 2004;Bland and Nielson, 1992). On the other hand, the adult lung is air-filled and maintains a "dry" state. The apical surface is covered by a thin layer of alveolar surface fluid. This layer of fluid is required for the proper air exchange and airway defenses. Cl − channels are also essential for maintaining the composition and volume of the alveolar surface fluid (Brochiero et al., 2004 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Several Cl − channels have previously been studied in the lung. The cystic fibrosis transmembrane conductance regulator (CFTR) (Harris et al., 1991), the voltage-gated Cl − channels, ClC2 (Thiemann et al., 1992), ClC3 (Lamb et al., 2001), and ClC5 (Edmonds et al., 2002, and Na + -K + -Cl − cotransporter (NKCC) (Rochelle et al., 2000) have been detected in fetal lungs, distal airway epithelial cells and alveolar epithelial cells. Some of the channels have been shown to be involved in fluid homeostasis i...

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Na⁺‐K⁺‐2Cl⁻Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia

Delpire¹,

Gagnon²

2018

Comprehensive Physiology

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Two genes encode the Na -K -2Cl cotransporters, NKCC1 and NKCC2, that mediate the tightly coupled movement of 1Na , 1K , and 2Cl across the plasma membrane of cells. Na -K -2Cl cotransport is driven by the chemical gradient of the three ionic species across the membrane, two of them maintained by the action of the Na /K pump. In many cells, NKCC1 accumulates Cl above its electrochemical potential equilibrium, thereby facilitating Cl channel-mediated membrane depolarization. In smooth muscle cells, this depolarization facilitates the opening of voltage-sensitive Ca channels, leading to Ca influx, and cell contraction. In immature neurons, the depolarization due to a GABA-mediated Cl conductance produces an excitatory rather than inhibitory response. In many cell types that have lost water, NKCC is activated to help the cells recover their volume. This is specially the case if the cells have also lost Cl . In combination with the Na /K pump, the NKCC's move ions across various specialized epithelia. NKCC1 is involved in Cl -driven fluid secretion in many exocrine glands, such as sweat, lacrimal, salivary, stomach, pancreas, and intestine. NKCC1 is also involved in K -driven fluid secretion in inner ear, and possibly in Na -driven fluid secretion in choroid plexus. In the thick ascending limb of Henle, NKCC2 activity in combination with the Na /K pump participates in reabsorbing 30% of the glomerular-filtered Na . Overall, many critical physiological functions are maintained by the activity of the two Na -K -2Cl cotransporters. In this overview article, we focus on the functional roles of the cotransporters in nonpolarized cells and in epithelia. © 2018 American Physiological Society. Compr Physiol 8:871-901, 2018.

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Liquid and Ion Transport by Fetal Airway and Lung Epithelia of Mice Deficient in Sodium-Potassium-2-Chloride Transporter

Cited by 37 publications

References 40 publications

Basolateral Cl⁻uptake mechanisms in Xenopus laevis lung epithelium

Basolateral Cl⁻uptake mechanisms in Xenopus laevis lung epithelium

Ionotropic GABA receptor expression in the lung during development

Na⁺‐K⁺‐2Cl⁻Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia

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Liquid and Ion Transport by Fetal Airway and Lung Epithelia of Mice Deficient in Sodium-Potassium-2-Chloride Transporter

Cited by 37 publications

References 40 publications

Basolateral Cl−uptake mechanisms in Xenopus laevis lung epithelium

Basolateral Cl−uptake mechanisms in Xenopus laevis lung epithelium

Ionotropic GABA receptor expression in the lung during development

Na+‐K+‐2Cl−Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia

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Basolateral Cl⁻uptake mechanisms in Xenopus laevis lung epithelium

Basolateral Cl⁻uptake mechanisms in Xenopus laevis lung epithelium

Na⁺‐K⁺‐2Cl⁻Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia