The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation

Endothelial ion signaling is crucial for the proper function of the arterial microcirculation, regulating local blood flow to meet metabolic demands and contributing to the regulation of systemic arterial pressure. The role of endothelial ion channels in the precise control of vascular resistance has been primarily investigated in animal models, where the microvasculature is more readily accessible. This review aims to discuss current knowledge on the role of endothelial ion signaling in vasomotor regulation in the human microcirculation, focusing on potassium (K⁺) channels (K_IR2.1, K_ATP, SK_Ca/IK_Ca), Transient Receptor Potential (TRP) channels, particularly TRP Vanilloid 1 (TRPV1) and TRPV4, and Piezo1 channels. The analysis examines the organization of the endothelial ionic signaling machinery in the most extensively studied human microvascular beds, such as the skin, skeletal muscle, and brain, while also discussing vascular reactivity in vessels isolated ex vivo. Accumulating evidence indicates that a distinct repertoire of endothelial ion channels engages diverse endothelium-dependent vasorelaxant pathways across different vascular beds. Understanding how endothelial channels regulate the microvascular unit is predicted to foster the search for alternative therapeutic strategies for treating cardiovascular and neurodegenerative disorders associated with endothelial dysfunction.