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Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses

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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 Ca2+-activated K+ channels channels by InsP3-induced Ca2+ release from the endoplasmic reticulum and/or store-operated Ca2+ 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.

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Acknowledgements

The authors own work referred to in this article was supported by the Deutsche Forschungsgemeinschaft (to CdW) and the British Heart Foundation and the Medical Research Council (to TMG).

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  1. Institut für Physiologie, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Cor de Wit

  2. Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

    Tudor M. Griffith

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de Wit, C., Griffith, T.M. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflugers Arch - Eur J Physiol 459, 897–914 (2010). https://doi.org/10.1007/s00424-010-0830-4

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