Does TRPC3 macrodominate the myoendothelial gap junction microdomain?

Abstract

This editorial refers to ‘Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity’ by S. Senadheera et al ., pp. 439–447, this issue. In 1998, Griffith and colleagues1 proposed that myoendothelial gap junctions (MEGJs) play a central role in endothelium-dependent hyperpolarization (EDH), the key mechanism coupling the activation of the endothelium by shear stress and blood borne-stimuli to vasodilation in the resistance vasculature. They envisioned that MEGJs, which are found at the ends of endothelial cell (EC) projections that protrude through holes in the internal elastic lamina of arteries and arterioles and link the EC to adjacent vascular smooth muscle cells (VSMCs), enabled EDH by acting as low-resistance pathways allowing the flow of hyperpolarizing current from the endothelium to the adjacent smooth muscle. Subsequently, however, it has become apparent that far from merely providing a locus for MEGJ, myoendothelial projections (MEPs) are unique microdomains that are capable of generating localized Ca2+ signals.2 This may enable them to influence the flow of information between ECs and VSMCs and also probably allows them to play a pivotal active role in triggering EDH ( Figure 1 ). Figure 1 Signalling components and pathways within myoendothelial projections which may contribute to endothelium-dependent hyperpolarization and myoendothelial feedback. The illustrated scheme is speculative, but is consistent with proposals and results described in a number of the references listed. See text for abbreviations and a more detailed explanation. In the current …