Journal
FRONTIERS IN PHYSIOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2020.598779
Keywords
pharmacology; vascular biology; endothelial cell; K(V)7 channel; K-IR channel; carbachol
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Funding
- British Heart Foundation [FS/18/41/33762]
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Background and Purpose: Arterial diameter is dictated by the contractile state of the vascular smooth muscle cells (VSMCs), which is modulated by direct and indirect inputs from endothelial cells (ECs). Modulators of KCNQ-encoded k(V)7 channels have considerable impact on arterial diameter and these channels are known to be expressed in VSMCs but not yet defined in ECs. However, expression of k(V)7 channels in ECs would add an extra level of vascular control. This study aims to characterize the expression and function of K(V)7 channels within rat mesenteric artery ECs. Experimental Approach: In rat mesenteric artery, KCNQ transcript and K(V)7 channel protein expression were determined via RT-qPCR, immunocytochemistry, immunohistochemistry and immunoelectron microscopy. Wire myography was used to determine vascular reactivity. Key Results: KCNQ transcript was identified in isolated ECs and VSMCs. K(V)7.1, K(V)7.4 and K(V)7.5 protein expression was determined in both isolated EC and VSMC and in whole vessels. Removal of ECs attenuated vasorelaxation to two structurally different K(V)7.2-5 activators S-1 and ML213. K(IR)2 blockers ML133, and BaCl2 also attenuated S-1 or ML213-mediated vasorelaxation in an endothelium-dependent process. K(V)7 inhibition attenuated receptor-dependent nitric oxide (NO)-mediated vasorelaxation to carbachol, but had no impact on relaxation to the NO donor, SNP. Conclusion and Implications: In rat mesenteric artery ECs, K(V)7.4 and K(V)7.5 channels are expressed, functionally interact with endothelial K(IR)2.x channels and contribute to endogenous eNOS-mediated relaxation. This study identifies K(V)7 channels as novel functional channels within rat mesenteric ECs and suggests that these channels are involved in NO release from the endothelium of these vessels.
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