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Titel:Rolle von TRPM8 und TRPA1 Kanälen bei der Regulation des Gefäßtonus
Autor:Kurtz, Felix
Weitere Beteiligte: Köhler, Ralf (Dr.)
Veröffentlicht:2011
URI:https://archiv.ub.uni-marburg.de/diss/z2011/0791
URN: urn:nbn:de:hebis:04-z2011-07918
DOI: https://doi.org/10.17192/z2011.0791
DDC: Medizin
Titel (trans.):Role of TRPM8 and TRPA1 channels for the regulation of the vascular tone
Publikationsdatum:2011-12-19
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Gefäßtonus, ion-channels, Ionenkanäle, vascular-tone ,, TRP, TRPM8, Patch-Clamp-Methode, TRPA1, gap-junctions, TRP-Kanäle, Elektrophysiologie, Endothel, EDHF, vessel

Zusammenfassung:
Über den endothelabhängigen Hyperpolarisation-Faktor (EDHF) induziert das Gefäßendothel eine Hyperpolarisation der direkt benachbarten Gefäßmuskelzellen und bewirkt so deren Relaxation. Gleichwohl die chemische Idendität des EDHF noch nicht geklärt ist, geht man davon aus, dass die EDHF Wirkung zunächst durch eine Aktivierung calciumregulierter Kaliumkanäle (KCa) im Endothel initiiert wird. Der hierfür erforderliche Anstieg der lokalen Calciumkonzentration in der Umgebung von KCa Kanälen kann über verschiedene Signalwege induziert werden. Ein bedeutsamer Weg dabei ist die Aktivierung von plasmalemmalen Kationenkanälen aus der Transient-Rezeptor-Potential (TRP)- Kanalfamilie, welche einen lokalen transmembranären Calciumeinstrom ermöglichen. Aufgrund präliminärer Literaturhinweise auf eine mögliche bedeutsame Rolle von TRPM8 und TRPA1 Kanälen für die endothelvermittelte Gefäßdilatation wurde in dieser Arbeit die Funktion dieser Kanäle als potentielle EDHF Induktoren pharmakologisch und elektrophysiologisch charakterisiert. Dazu wurde zunächst die Wirkung etablierter TRMP8 Aktivatoren (Menthol und Icilin) und eines TRPA1 Aktivators (AITC) auf den Gefäßwiderstand isoliert perfundierter Ateriae carotides der Maus untersucht. Alle genannten Substanzen induzierten konzentrationsabhängig Dilatationen, in unterschiedlichem Ausmaß, wobei die stärkste Dilatation mit Icilin zu beobachten war. Die gefäßdilatierende Wirkung dieser Substanzen blieb allerdings auch nach mechanischer Endotheldenudierung erhalten, was für eine endothelunabhängige Dilatation spricht. In Einklang damit konnten mit den genannten TRP-Kanalaktivatoren auch keine TRP-charakteristischen Transmembranströme in isolierten Endothelzellen aus den Arteriae carotides induziert werden, was gegen eine wesentliche funktionelle Rolle von TRMP8 und TRPA1 Kanälen in Endothelzellen spricht. Beobachtet wurde die Aktivierung eines kräftigen Kationenausstromes durch Menthol in isolierten Endothelzellen, sowie eine nahezu komplette Hemmung eines Kationeneinstromes (wahrscheinlich L-Typ Calciumkanäle) durch Menthol in kultivierten glatten Gefäßmuskelzellen (A7R5 Zellen). Die Hemmung der L-Typ Calciumkanäle durch Menthol könnte eine Erklärung für endothelunabhängige vasodilatierende Wirkung von Menthol bieten. Eine Beteiligung endothelialer TRPM8 und TRPA1 Kanäle bei der Regulation des Gefäßtonus konnte allerdings im Rahmen dieser Arbeit nicht bestätigt werden.

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