Figure 3.

The vasodilator signalling mechanism at myoendothelial contact sites in rat mesenteric artery. At sites of close contact between the endothelium and smooth muscle, localized gap junction connexins (Cx), endoplasmic reticulum (ER) 1,4,5-triphosphate receptors (IP₃R), and intermediate-conductance calcium-activated potassium channels (IK_Ca) occur in close proximity to TRPC3. The localization and differential distribution of these channels and receptors suggests that these myoendothelial microdomains enable transfer of a connexin (Cx)-dependent endothelial hyperpolarizing current (1) and/or localized K⁺ activity (2 and 3), with the net effect being smooth muscle hyperpolarization and endothelium-dependent relaxation (modified from Sandow et al.;^7,34 see also Figure 1 and Supplementary material online, FigureS7). TRPC3-dependent calcium influx may activate myoendothelial K_Ca directly (i), and/or refill the IP₃R-mediated ER store (ii). Inward rectifying potassium channels (K_ir) are exclusive to the endothelium^6,13,55 and are activated by potassium in a feedback with K_Ca and Na⁺/K⁺-ATPase activity. DAG, diacylglycerol; E_m, membrane potential; MEGJ, myoendothelial gap junction; PLCβ, phospholipase C-beta; VDCC, voltage-dependent calcium channel.