| Online-Ressource |
Verfasst von: | Seyler, Claudia [VerfasserIn]  |
| Duthil-Straub, Elvenn [VerfasserIn]  |
| Zitron, Edgar [VerfasserIn]  |
| Gierten, Jakob [VerfasserIn]  |
| Scholz, Eberhard P. [VerfasserIn]  |
| Fink, Rainer [VerfasserIn]  |
| Karle, Christoph [VerfasserIn]  |
| Becker, Rüdiger [VerfasserIn]  |
| Katus, Hugo [VerfasserIn]  |
| Thomas, Dierk [VerfasserIn]  |
Titel: | TASK1 (K2P3.1) K+ channel inhibition by endothelin-1 is mediated through Rho kinase-dependent phosphorylation |
Verf.angabe: | C Seyler, E Duthil-Straub, E Zitron, J Gierten, EP Scholz, RHA Fink, CA Karle, R Becker, HA Katus, and D Thomas |
Jahr: | 2012 |
Jahr des Originals: | 2011 |
Umfang: | 9 S. |
Fussnoten: | Published online: 27 July 2011 ; 2P ist im Titel tief- und das Pluszeichen hochgestellt ; Gesehen am 18.07.2018 |
Titel Quelle: | Enthalten in: British journal of pharmacology |
Ort Quelle: | Malden, MA : Wiley, 1946 |
Jahr Quelle: | 2012 |
Band/Heft Quelle: | 165(2012), 5, Seite 1467-1475 |
ISSN Quelle: | 1476-5381 |
Abstract: | BACKGROUND AND PURPOSE: TASK1 (K2P3.1) two-pore-domain K+ channels contribute substantially to the resting membrane potential in human pulmonary artery smooth muscle cells (hPASMC), modulating vascular tone and diameter. The endothelin-1 (ET-1) pathway mediates vasoconstriction and is an established target of pulmonary arterial hypertension (PAH) therapy. ET-1-mediated inhibition of TASK1 currents in hPASMC is implicated in the pathophysiology of PAH. This study was designed to elucidate molecular mechanisms underlying inhibition of TASK1 channels by ET-1. EXPERIMENTAL APPROACH: Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record TASK1 currents from hPASMC and Xenopus oocytes. KEY RESULTS: ET-1 inhibited TASK1-mediated IKN currents in hPASMC, an effect attenuated by Rho kinase inhibition with Y-27632. In Xenopus oocytes, TASK1 current reduction by ET-1 was mediated by endothelin receptors ETA (IC50= 0.08 nM) and ETB (IC50= 0.23 nM) via Rho kinase signalling. TASK1 channels contain two putative Rho kinase phosphorylation sites, Ser336 and Ser393. Mutation of Ser393 rendered TASK1 channels insensitive to ETA- or ETB-mediated current inhibition. In contrast, removal of Ser336 selectively attenuated ETA-dependent TASK1 regulation without affecting the ETB pathway. CONCLUSIONS AND IMPLICATIONS: ET-1 regulated vascular TASK1 currents through ETA and ETB receptors mediated by downstream activation of Rho kinase and direct channel phosphorylation. The Rho kinase pathway in PASMC may provide a more specific therapeutic target in pulmonary arterial hypertension treatment. |
DOI: | doi:10.1111/j.1476-5381.2011.01626.x |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: http://dx.doi.org/10.1111/j.1476-5381.2011.01626.x |
| Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372730/ |
| DOI: https://doi.org/10.1111/j.1476-5381.2011.01626.x |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1577733789 |
Verknüpfungen: | → Zeitschrift |
TASK1 (K2P3.1) K+ channel inhibition by endothelin-1 is mediated through Rho kinase-dependent phosphorylation / Seyler, Claudia [VerfasserIn]; 2012 (Online-Ressource)