| Activation of endothelial and epithelial K(Ca) 2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles. | |
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MedLine Citation:
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PMID: 22506557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Small (K(Ca) 2) and intermediate (K(Ca) 3.1) conductance calcium-activated potassium channels (K(Ca) ) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of K(Ca) 2.3 and K(Ca) 3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries. EXPERIMENTAL APPROACH: Channel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. K(Ca) 2 and K(Ca) 3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole-cell patch clamp techniques. RESULTS: While K(Ca) 2.3 expression was similar, K(Ca) 3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive K(Ca) 2.3 and K(Ca) 3.1 proteins were found in both endothelium and epithelium. K(Ca) currents were present in HSAEpi cells and sensitive to the K(Ca) 2.3 blocker UCL1684 and the K(Ca) 3.1 blocker TRAM-34. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the K(Ca) 2.3/ K(Ca) 3.1 activator, NS309, induced concentration-dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the K(Ca) 2 channel blocker apamin, while the K(Ca) 3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01-1 µM). CONCLUSIONS AND IMPLICATIONS: K(Ca) 2.3 and K(Ca) 3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. K(Ca) 2.3 channels contributed to endo- and epithelium-dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease. |
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Authors:
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Christel Kroigaard; Thomas Dalsgaard; Gorm Nielsen; Britt E Laursen; Hans Pilegaard; Ralf Köhler; Ulf Simonsen |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 167 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-08-06 Completed Date: 2013-01-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 37-47 Citation Subset: IM |
Copyright Information:
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© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Faculty of Health Sciences, Aarhus University, Aarhus C, Denmark. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Bronchioles / drug effects*, physiology Cells, Cultured Endothelium / drug effects*, physiology Epithelial Cells / drug effects*, physiology Humans Indoles / pharmacology* Intermediate-Conductance Calcium-Activated Potassium Channels / agonists, physiology Middle Aged Oximes / pharmacology* Pulmonary Artery / drug effects*, physiology RNA, Messenger / metabolism Respiratory Mucosa / cytology Small-Conductance Calcium-Activated Potassium Channels / agonists, physiology* |
| Chemical | |
Reg. No./Substance:
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0/6,7-dichloro-1H-indole-2,3-dione 3-oxime; 0/Indoles; 0/Intermediate-Conductance Calcium-Activated Potassium Channels; 0/KCNN3 protein, human; 0/KCNN4 protein, human; 0/Oximes; 0/RNA, Messenger; 0/Small-Conductance Calcium-Activated Potassium Channels |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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