Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Nagaraj, C; Tang, B; Balint, Z; Wygrecka, M; Hrzenjak, A; Kwapiszewska, G; Stacher, E; Lindenmann, J; Weir, EK; Olschewski, H; Olschewski, A.
Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries.
Eur Respir J. 2013; 41(1):85-95
Doi: 10.1183/09031936.00211811
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- Leading authors Med Uni Graz
- Chandran Nagaraj
- Olschewski Andrea
- Co-authors Med Uni Graz
- Balint Zoltan
- Hrzenjak Andelko
- Kwapiszewska-Marsh Grazyna
- Lindenmann Jörg
- Olschewski Horst
- Stacher-Priehse Elvira
- Tang Bi
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Cells, Cultured -
- Humans -
- Myocytes, Smooth Muscle - metabolism
- Potassium Channels - physiology
- Pulmonary Artery - cytology Pulmonary Artery - enzymology Pulmonary Artery - physiology
- src-Family Kinases - physiology
- Find related publications in this database (Keywords)
- Pulmonary artery pressure
- resting membrane potential
- Src tyrosine kinase
- TWIK-related acid sensitive potassium-1 channel