title: Endothelium-Dependent Hyperpolarization and Endothelial Dysfunction.
abstract: The endothelium controls vascular tone not only by releasing various vasoactive substances but also by another pathway associated with the hyperpolarization of both endothelial and vascular smooth muscle cells and is termed endothelium-dependent hyperpolarization (EDH). These responses involve an increase in the endothelial intracellular Ca concentration by the activation of transient receptor potential channels (predominantly TRPV4) followed by the opening of Ca-activated K channels of small and intermediate conductance (SKCa and IKCa). These channels show a distinct subcellular distribution. SKCa are widely distributed over the plasma membrane but segregates at sites of homocellular endothelial junctions, whereas IKCa are preferentially expressed in the myoendothelial projections. Following KCa activation, smooth muscle hyperpolarization is evoked by electrical coupling through myoendothelial gap junctions and/or by the potassium efflux that subsequently activates smooth muscle Kir2.1 and/or Na/K-ATPase. Alteration of the EDH contributes to the endothelial dysfunctions observed in various pathologies or conversely compensates for the loss in NO bioavailability. A better characterization of EDH should allow determining whether new druggable targets can be identified for the treatment of cardiovascular diseases.
authors.affiliation: Unité de Recherche de Découverte Cardiovasculaire, Institut de Recherches Servier, Suresnes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Félétou
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000503:physiopathology; D017630:Connexins / Q000378:metabolism; D003920:Diabetes Mellitus / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D001685:Biological Factors; D015220:Calcium Channels; D017630:Connexins; D015221:Potassium Channels; D050916:TRPV Cation Channels; C067410:endothelium-dependent hyperpolarization factor