Home
Resources
Publications
Improvement of Endothelium-Dependent Vasodilations by SKA-31 and SKA-20, Activators of Small- And Intermediate-Conductance Ca2+ -Activated K+ -Channels

Improvement of Endothelium-Dependent Vasodilations by SKA-31 and SKA-20, Activators of Small- And Intermediate-Conductance Ca2+ -Activated K+ -Channels

A-L Hasenau, G Nielsen, C Morisseau, B D Hammock, H Wulff, R Köhler

Acta Physiol (Oxf). 2011 Sep;203(1):117-26.

PMID: 21362152

Abstract:

Aim:
Endothelial membrane hyperpolarization mediated by KCa3.1 and KCa2.3 channels has been demonstrated to initiate endothelium-derived hyperpolarizing factor (EDHF)-type vasodilations. Moreover, pharmacological potentiation of KCa3.1/KCa2.3 channels has been suggested to improve EDHF-type vasodilations. Herein, we determined whether the KCa3.1/KCa2.3 activator SKA-31 and its derivative SKA-20 improve endothelial dysfunction in KCa3.1-/- and NOS3-/- mice.
Methods:
Membrane potentials were measured using patch-clamp electrophysiology on carotid artery (CA) endothelial cells (CAEC) from wild-type (wt) and KCa3.1-/- mice. Endothelium-dependent vasodilations were determined by pressure myography in CA.
Results:
SKA-31 (1 μm) activated KCa3.1 and KCa2.3 channels and induced membrane hyperpolarization in CAEC of wt (ΔMP -45 mV). These responses were significantly reduced in CAEC of KCa3.1-/- (ΔMP -8 mV). SKA-31 (200 nm, 500 nm) and SKA-20 (300 nm) significantly enhanced EDHF vasodilations in wt. SKA-20 also improved vasodilations during NO synthesis. In KCa3.1-/-, the defective EDHF vasodilations were unchanged at 200 nm SKA-31, but were significantly improved at 500 nm. EDHF vasodilations were slightly enhanced at 300 nm SKA-20, but vasodilations during NO synthesis were unchanged. SKA-31 (500 nm) enhanced the impaired endothelium-dependent vasodilation in NOS3-/- mice twofold. Pharmacological inhibition of the soluble epoxide hydrolase by t-AUCB (1 μm) in contrast did not increase ACh-induced EDHF- or NO-mediated vasodilations in wt and KCa3.1-/-.
Conclusion:
Normal and defective endothelium-dependent vasodilations in murine carotid arteries can be improved by pharmacological enhancement of KCa3.1/KCa2.3 functions. These findings further support the concept that pharmacological activation of endothelial KCa2.3/KCa3.1 could offer a novel endothelium-specific antihypertensive strategy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP40172654	SKA-31		40172-65-4	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: