title: Endothelium-derived hyperpolarising factors and associated pathways: a synopsis.
abstract: The term endothelium-derived hyperpolarising factor (EDHF) was introduced in 1987 to describe the hypothetical factor responsible for myocyte hyperpolarisations not associated with nitric oxide (EDRF) or prostacyclin. Two broad categories of EDHF response exist. The classical EDHF pathway is blocked by apamin plus TRAM-34 but not by apamin plus iberiotoxin and is associated with endothelial cell hyperpolarisation. This follows an increase in intracellular [Ca(2+)] and the opening of endothelial SK(Ca) and IK(Ca) channels preferentially located in caveolae and in endothelial cell projections through the internal elastic lamina, respectively. In some vessels, endothelial hyperpolarisations are transmitted to myocytes through myoendothelial gap junctions without involving any EDHF. In others, the K(+) that effluxes through SK(Ca) activates myocytic and endothelial Ba(2+)-sensitive K(IR) channels leading to myocyte hyperpolarisation. K(+) effluxing through IK(Ca) activates ouabain-sensitive Na(+)/K(+)-ATPases generating further myocyte hyperpolarisation. For the classical pathway, the hyperpolarising "factor" involved is the K(+) that effluxes through endothelial K(Ca) channels. During vessel contraction, K(+) efflux through activated myocyte BK(Ca) channels generates intravascular K(+) clouds. These compromise activation of Na(+)/K(+)-ATPases and K(IR) channels by endothelium-derived K(+) and increase the importance of gap junctional electrical coupling in myocyte hyperpolarisations. The second category of EDHF pathway does not require endothelial hyperpolarisation. It involves the endothelial release of factors that include NO, HNO, H(2)O(2) and vasoactive peptides as well as prostacyclin and epoxyeicosatrienoic acids. These hyperpolarise myocytes by opening various populations of myocyte potassium channels, but predominantly BK(Ca) and/or K(ATP), which are sensitive to blockade by iberiotoxin or glibenclamide, respectively.
authors.affiliation: Faculty of Life Sciences, University of Manchester, CTF Building, 46 Grafton St, Manchester, M13 9NT, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Edwards
authors.forename: Michel
authors.initials: M
authors.lastname: Félétou
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Weston
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D002248:Carbon Monoxide / Q000502:physiology; D015777:Eicosanoids / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology*; D011464:Epoprostenol / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D032342:Muscle Cells / Q000502:physiology; D020098:Natriuretic Peptide, C-Type / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D011188:Potassium / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011720:Pyrazoles; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
chemical_list: D001685:Biological Factors; D015777:Eicosanoids; D045462:Endothelium-Dependent Relaxing Factors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011720:Pyrazoles; D051640:Small-Conductance Calcium-Activated Potassium Channels; C411671:TRAM 34; C067410:endothelium-dependent hyperpolarization factor; D020098:Natriuretic Peptide, C-Type; D001030:Apamin; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006861:Hydrogen Peroxide; D011464:Epoprostenol; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium
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