gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Selective Inhibition of endothelial IKCa1 and SKCa3 K+ channels prevents EDHF-mediated vasodilation

Selektive Inhibition endothelialer IKCa1 und SKCa3 K+-Kanäle unterdrückt die EDHF-vermittelte Vasodilatation

Meeting Abstract

  • R. Köhler - Philipps-Universität Marburg (Marburg, D)
  • I. Grgic - Philipps-Universität Marburg (Marburg, D)
  • T. Maier - Philipps-Universität Marburg (Marburg, D)
  • C. Busch - Philipps-Universität Marburg (Marburg, D)
  • J. Hoyer - Philipps-Universität Marburg (Marburg, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP136

The electronic version of this article is the complete one and can be found online at:

Published: August 8, 2006

© 2006 Köhler et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Activation of Ca2+-activated K+ channels (KCa) has been suggested to play a key role in endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation. However, it is still elusive which KCa mediate cell hyperpolarization and thus EDHF-mediated vasodilation. Using the new non-cytochrome P450 blocking clotrimazole-derivatives, TRAM-34 and TRAM-39 as highly selective inhibitors of the intermediate-conductance KCa (IKCa1) and apamin, a blocker of the small-conductance KCa (rSKCa3), we investigated the functional role IKCa1 and SKCa3 in endothelial hyperpolarization of human mesenteric and rat carotid artery as well as EDHF-mediated vasodilation. Expression and function of the rIKCa1 and rSKCa3 were detected in situ in single endothelial cells of human mesenteric artery (hMA)and rat carotid arteries (rCA) by whole-cell patch-clamp measurements and single-cell RT-PCR. rIKCa1 currents were blocked by charybdotoxin (ChTx), clotrimazole (CLT), TRAM-34, or by TRAM-39, while rSK3 was blocked by apamin. In in-situ measurements of endothelilal membrane potential in hMA and rCA, hyperpolarization in response to bradykinin and acetylcholine, respectively, was abolished by the combination of apamin (APA) and TRAM-34 or apamin and ChTx. In phenylephrine-preconstricted rat CA, EDHF-mediated vasodilation was almost completely blocked by ChTX, CLT, TRAM-34, or TRAM-39 in combination with APA. APA and CLT alone or sulphaphenzole, a blocker of the cytochrome P450 isoform 2C9, were ineffective in blocking the EDHF-response.

In conclusion, activation of both KCa, IKCa1 and SKCa3 in the endothelium of rCA and hMA is crucial in mediating endothelial hyperpolarization and thus generation of the EDHF-signal.