AUTHOR=Baldwin Samuel N. , Sandow Shaun L. , Mondéjar-Parreño Gema , Stott Jennifer B. , Greenwood Iain A. 

TITLE=KV7 Channel Expression and Function Within Rat Mesenteric Endothelial Cells

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.598779

DOI=10.3389/fphys.2020.598779

ISSN=1664-042X

ABSTRACT=<p><bold>Background and Purpose:</bold> 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<sub>V</sub>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<sub>V</sub>7 channels in ECs would add an extra level of vascular control. This study aims to characterize the expression and function of K<sub>V</sub>7 channels within rat mesenteric artery ECs.</p><p><bold>Experimental Approach:</bold> In rat mesenteric artery, KCNQ transcript and K<sub>V</sub>7 channel protein expression were determined via RT-qPCR, immunocytochemistry, immunohistochemistry and immunoelectron microscopy. Wire myography was used to determine vascular reactivity.</p><p><bold>Key Results:</bold> KCNQ transcript was identified in isolated ECs and VSMCs. K<sub>V</sub>7.1, K<sub>V</sub>7.4 and K<sub>V</sub>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<sub>V</sub>7.2-5 activators S-1 and ML213. K<sub>IR</sub>2 blockers ML133, and BaCl<sub>2</sub> also attenuated S-1 or ML213-mediated vasorelaxation in an endothelium-dependent process. K<sub>V</sub>7 inhibition attenuated receptor-dependent nitric oxide (NO)-mediated vasorelaxation to carbachol, but had no impact on relaxation to the NO donor, SNP.</p><p><bold>Conclusion and Implications:</bold> In rat mesenteric artery ECs, K<sub>V</sub>7.4 and K<sub>V</sub>7.5 channels are expressed, functionally interact with endothelial K<sub>IR</sub>2.x channels and contribute to endogenous eNOS-mediated relaxation. This study identifies K<sub>V</sub>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.</p>