title: Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses.
abstract: It is becoming increasingly evident that electrical signaling via gap junctions plays a central role in the physiological control of vascular tone via two related mechanisms (1) the endothelium-derived hyperpolarizing factor (EDHF) phenomenon, in which radial transmission of hyperpolarization from the endothelium to subjacent smooth muscle promotes relaxation, and (2) responses that propagate longitudinally, in which electrical signaling within the intimal and medial layers of the arteriolar wall orchestrates mechanical behavior over biologically large distances. In the EDHF phenomenon, the transmitted endothelial hyperpolarization is initiated by the activation of Ca(2+)-activated K(+) channels channels by InsP(3)-induced Ca(2+) release from the endoplasmic reticulum and/or store-operated Ca(2+) entry triggered by the depletion of such stores. Pharmacological inhibitors of direct cell-cell coupling may thus attenuate EDHF-type smooth muscle hyperpolarizations and relaxations, confirming the participation of electrotonic signaling via myoendothelial and homocellular smooth muscle gap junctions. In contrast to isolated vessels, surprisingly little experimental evidence argues in favor of myoendothelial coupling acting as the EDHF mechanism in arterioles in vivo. However, it now seems established that the endothelium plays the leading role in the spatial propagation of arteriolar responses and that these involve poorly understood regenerative mechanisms. The present review will focus on the complex interactions between the diverse cellular signaling mechanisms that contribute to these phenomena.
authors.affiliation: Institut für Physiologie, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. dewit@uni-luebeck.de
authors.forename: Cor
authors.initials: C
authors.lastname: de Wit
authors.forename: Tudor M
authors.initials: TM
authors.lastname: Griffith
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D017630:Connexins / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D000242:Cyclic AMP / Q000819:agonists; D015777:Eicosanoids / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D015398:Signal Transduction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D001685:Biological Factors; D017630:Connexins; D015777:Eicosanoids; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D007473:Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D051640:Small-Conductance Calcium-Activated Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D006861:Hydrogen Peroxide; D000242:Cyclic AMP