| Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. | |
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MedLine Citation:
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PMID: 22523355 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The potassium channel TASK-1, together with other potassium channels controls the low resting tone of pulmonary arteries. The Src family tyrosine kinase (SrcTK) may control potassium channel function in human pulmonary artery smooth muscle cells (hPASMCs) in response to changes in oxygen tension and the clinical use of an SrcTK inhibitor has resulted in partly reversible pulmonary hypertension. This study aimed to determine the role of SrcTK for hypoxia-induced inhibition of potassium channels in hPASMCs.We show that SrcTK is colocalized with the TASK-1 channel. Inhibition of SrcTK decreases potassium current density and results in considerable depolarization, while activation of SrcTK increases potassium current in patch-clamp recordings. Moderate hypoxia and the SrcTK-inhibitor decrease the tyrosine-phosphorylation state of the TASK-1 channel. Hypoxia also decreases the level of phospho-SrcTK (tyr419) and reduces the co-localization of the TASK-1 channel and phospho-SrcTK. Corresponding to this, hypoxia reduces TASK-1 currents before but not after SrcTK inhibition and, in the isolated perfused mouse lung, SrcTK inhibitors increase pulmonary arterial pressure.We propose that the Src family tyrosine kinase is a crucial factor controlling potassium channels, acting as a cofactor for setting a negative resting membrane potential in hPASMCs and a low resting pulmonary vascular tone. |
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Authors:
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Chandran Nagaraj; Bi Tang; Zoltán Bálint; Malgorzata Wygrecka; Andelko Hrzenjak; Grazyna Kwapiszewska; Elvira Stacher; Joerg Lindenmann; E Kenneth Weir; Horst Olschewski; Andrea Olschewski |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-20 |
Journal Detail:
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Title: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology Volume: - ISSN: 1399-3003 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8803460 Medline TA: Eur Respir J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Graz, Austria. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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