ArticleAmerican journal of respiratory cell and molecular biology2013
Ca(2+)-activated K(+) channel-3.1 blocker TRAM-34 attenuates airway remodeling and eosinophilia in a murine asthma model.
Article in American journal of respiratory cell and molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Potassium Channels of the Airway Epithelium.Acta physiologica (Oxford, England) · 2026Review
- KCNJ2 is Required for NLRP3 Inflammasome Activation That Drives Allergic Airway Inflammation and Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrating GPCR Regulation and Calcium Dynamics in Airway Smooth Muscle Function: A Comprehensive Review.Cells · 2026Review
- Ion Channels in the Immune Response of Asthma.Journal of respiratory biology and translational medicine · 2024Article
- Pulmonary adaptation to repeated poly(I:C) exposure is impaired in asthmatic mice: an observational study.Respiratory research · 2024Article
- Efficacy of combined tumor irradiation and KScientific reports · 2023Article
- A review of the pathophysiology and the role of ion channels on bronchial asthma.Frontiers in pharmacology · 2023Review
- Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations.Frontiers in pharmacology · 2021Review
- Article
- CaBritish journal of pharmacology · 2020Review
- Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.Annual review of pharmacology and toxicology · 2020Review
- A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis.Scientific reports · 2018Article
- KCa3.1 Channel Modulators as Potential Therapeutic Compounds for Glioblastoma.Current neuropharmacology · 2018Article
- Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore.Molecular pharmacology · 2017Article
- The potassium channel KCa3.1 constitutes a pharmacological target for neuroinflammation associated with ischemia/reperfusion stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Article
- Lentiviral shRNA against KCa3.1 inhibits allergic response in allergic rhinitis and suppresses mast cell activity via PI3K/AKT signaling pathway.Scientific reports · 2015Article
- Ion channels in innate and adaptive immunity.Annual review of immunology · 2015Review
- Human lung myofibroblast TGFβ1-dependent Smad2/3 signalling is Ca(2+)-dependent and regulated by KCa3.1 K(+) channels.Fibrogenesis & tissue repair · 2015Article
- Article
- Functional KCa3.1 channels regulate steroid insensitivity in bronchial smooth muscle cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Key features of asthma include bronchial hyperresponsiveness (BHR), eosinophilic airway inflammation, and bronchial remodeling, characterized by subepithelial collagen deposition, airway fibrosis, and increased bronchial smooth muscle (BSM) mass. The calcium-activated K(+) channel K(Ca)3.1 is expressed by many cells implicated in the pathogenesis of asthma, and is involved in both inflammatory and remodeling responses in a number of tissues. The specific K(Ca)3.1 blocker 5-[(2-chlorophenyl)(diphenyl)methyl]-1H-pyrazole (TRAM-34) attenuates BSM cell proliferation, and both mast cell and fibrocyte recruitment in vitro. We aimed to examine the effects of K(Ca)3.1 blockade on BSM remodeling, airway inflammation, and BHR in a murine model of chronic asthma. BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) on Days 0 and 14, and then challenged with intranasal OVA during Days 14-75. OVA-sensitized/challenged mice received TRAM-34 (120 mg/kg/day, subcutaneous) from Days -7 to 75 (combined treatment), Days -7 to 20 (preventive treatment), or Days 21 to 75 (curative treatment). Untreated mice received daily injections of vehicle (n = 8 per group). Bronchial remodeling was assessed by histological and immunohistochemical analyses. Inflammation was evaluated using bronchoalveolar lavage and flow cytometry. We also determined BHR in both conscious and anesthetized mice via plethysmography. We demonstrated that curative treatment with TRAM-34 abolishes BSM remodeling and subbasement collagen deposition, and attenuates airway eosinophilia. Although curative treatment alone did not significantly reduce BHR, the combined treatment attenuated nonspecific BHR to methacholine. This study indicates that K(Ca)3.1 blockade could provide a new therapeutic strategy in asthma.
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