ArticleRespiratory research2010
K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport.
Article in Respiratory research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury.Scientific reports · 2016Pooled it
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- Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome.Journal of nanobiotechnology · 2022Article
- Impact of KvLQT1 potassium channel modulation on alveolar fluid homeostasis in an animal model of thiourea-induced lung edema.Frontiers in physiology · 2022Article
- Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway.Respiratory research · 2021Article
- Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential.Frontiers in pharmacology · 2021Review
- Bone marrow mesenchymal stem cells derived miRNA-130b enhances epithelial sodium channel by targeting PTEN.Respiratory research · 2020Article
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- Ion transport mechanisms for smoke inhalation-injured airway epithelial barrier.Cell biology and toxicology · 2020Article
- Plasmin improves blood-gas barrier function in oedematous lungs by cleaving epithelial sodium channels.British journal of pharmacology · 2020Article
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- Novel mechanisms for crotonaldehyde-induced lung edema.Oncotarget · 2017Article
- Involvement of CaBioscience reports · 2017Article
- Formaldehyde impairs transepithelial sodium transport.Scientific reports · 2016Article
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- Pulmonary epithelial barrier function: some new players and mechanisms.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- A role for two-pore K⁺ channels in modulating Na⁺ absorption and Cl⁻ secretion in normal human bronchial epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate-Na stimulates human alveolar fluid clearance by releasing external Na+ self-inhibition of epithelial Na+ channels.American journal of respiratory cell and molecular biology · 2011Article
- Cpt-cAMP activates human epithelial sodium channels via relieving self-inhibition.Biochimica et biophysica acta · 2011Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundLung epithelial Na+ channels (ENaC) are regulated by cell Ca2+ signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K+ channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K+ channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport.
methodsVerapamil-induced depression of heterologously expressed human alphabetagamma ENaC in Xenopus oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and in vivo alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca2+ signal in H441 cells was analyzed using Fluo 4AM.
resultsThe rate of in vivo AFC was reduced significantly (40.6+/-6.3% of control, P<0.05, n=12) in mice intratracheally administrated verapamil. KCa3.1 (1-EBIO) and KATP (minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca2+ signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2+ in alphabetagamma ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, KV (pyrithione-Na), K Ca3.1 (1-EBIO), and KATP (minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na+ and K+ transport pathways.
conclusionsOur observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal.
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