KV7 Channel Expression and Function Within Rat Mesenteric Endothelial Cells

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 BaCl 2 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.