Document Detail


Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries.
MedLine Citation:
PMID:  22523355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The potassium channel TWIK-related acid sensitive potassium (TASK)-1 channel, 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 a SrcTK inhibitor has resulted in partly reversible pulmonary hypertension. This study aimed to determine the role of SrcTK in hypoxia-induced inhibition of potassium channels in hPASMCs. We show that SrcTK is co-localised with the TASK-1 channel. Inhibition of SrcTK decreases potassium current density and results in considerable depolarisation, 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-localisation 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 SrcTK 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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-04-20
Journal Detail:
Title:  The European respiratory journal     Volume:  41     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-06-13     Revised Date:  2013-10-15    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  85-95     Citation Subset:  IM    
Affiliation:
Ludwig Boltzmann Institute for Lung Vascular Research, Medical University of Graz, Austria.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Humans
Myocytes, Smooth Muscle / metabolism
Potassium Channels / physiology*
Pulmonary Artery / cytology,  enzymology,  physiology*
src-Family Kinases / physiology*
Grant Support
ID/Acronym/Agency:
R01 HL 65322/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Potassium Channels; EC 2.7.10.2/src-Family Kinases
Comments/Corrections
Comment In:
Eur Respir J. 2013 Sep;42(3):869-70   [PMID:  24000257 ]
Eur Respir J. 2013 Jan;41(1):3-4   [PMID:  23277514 ]

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