Endothelium-Derived Hyperpolarization in Vascular Physiology
Summary
Endothelium-derived hyperpolarization (EDH) is a fundamental mechanism by which the vascular endothelium regulates vessel tone and tissue perfusion, particularly in resistance arteries. Upon stimulation by chemical agonists or shear stress, endothelial cells undergo a rise in intracellular calcium that activates specialised potassium channels. The resulting efflux of K+ ions hyperpolarises the endothelial membrane, a change that can spread via gap junctions to adjacent smooth muscle cells, causing relaxation. This pathway operates alongside nitric oxide and prostacyclin signalling, and predominates in smaller vessels where electrical coupling and microdomain signalling at myoendothelial junctions are highly efficient. EDH underpins fine control of blood pressure and regional blood flow, and its impairment is implicated in hypertension, diabetes and ageing. Advances in imaging, electrophysiology and computational modelling have elucidated the interplay between Ca2+-permeable channels, small- and intermediate-conductance Ca2+-activated K+ channels and inward-rectifier K+ channels. Understanding EDH at cellular, network and whole-vessel levels promises new therapeutic approaches to restore endothelial function in cardiovascular disease.
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Endothelium-Derived Hyperpolarization in Vascular Physiology publication trend
The graph below shows the total number of articles in endothelium-derived hyperpolarization in vascular physiology across all publications each year (not limited to Nature Index journals).
Technical terms
Endothelium-derived hyperpolarization (EDH): A vasodilator mechanism whereby endothelial activation leads to K+ channel-mediated membrane hyperpolarization that relaxes adjacent smooth muscle.
Small- and intermediate-conductance Ca2+-activated K+ channels (SKCa, IKCa): Endothelial potassium channels activated by rises in intracellular Ca2+, essential for initiating EDH.
Inward-rectifier K+ channel (Kir2.1): A K+ channel that amplifies and sustains endothelial hyperpolarization, contributing to vessel dilation.
Myoendothelial junction (MEJ): Specialized microdomain where endothelial projections contact smooth muscle cells, enabling targeted signal transfer during EDH.
Gap junction: Protein channels connecting adjacent cells to permit electrical coupling and spread of hyperpolarization along the vessel wall.
References
- On the Ca2+ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach. Computers in Biology and Medicine (2023).
- Polarized localization of phosphatidylserine in endothelium regulates Kir2.1. JCI Insight (2023).
- Endothelial Ion Channels and Cell-Cell Communication in the Microcirculation. Frontiers in Physiology (2022).
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