Stimulation of the endothelium modulates arterial diameter. Spontaneous, agonist-mediated and physical forces can each activate endothelial cell Ca2+ events. These can in turn activate Ca2+ -dependent processes leading to dilation, such as the formation of nitric oxide (NO) and stimulation of Ca2+ -activated K+ (KCa) channels. There is emerging evidence that the Ca2+ events within endothelial cells have distinct patterns and often occur within microdomains. One such domain is the endothelial cell projects towards smooth muscle cells, termed myoendothelial junctions. Here gap junctions (MEGJs) enable the movement of current and small molecules between the two cell types. This proximity enables heterocellular influences, which can occur either via the diffusion of factors and/or by intercellular coupling. For example, the efflux of K+ through KCa channels in the projection can diffuse and activate smooth muscle inwardly rectifying K+ channels and Na+/K+ -ATPases, K+ acting as a diffusible hyperpolarizing factor (EDHF); and/or the ensuing hyperpolarizing current can directly pass to smooth muscle (EDH). Within the endothelial cell projection a multitude of other proteins are congregated, including inositol trisphosphate receptors and transient receptor potential (TRP) cation channels. TRPV4 channels are expressed here, and when activated at low pressure, Ca2+ influx can oppose myogenic tone via NO and EDH. There are effectively no voltage-gated Na+, Ca2+ or K+ channels in endothelial cells from most vascular beds, hence there is little effect of depolarization on endothelial cell Ca2+ events. However, from resting potentials in intact arteries and arterioles, hyperpolarization of endothelial cells in response to agonists can in itself stimulate an increase in Ca2+ event frequency at discreet sites within endothelial cells. This process can act to amplify dilation, but can also contribute to the propagation of hyperpolarizing current through the arterial wall, which leads to conducted dilation. Within the microcirculation, conducted dilation is observed to agonists that hyperpolarize endothelial and smooth muscle cells and relies on functional MEGJs. The endothelium acts as the conduit for longitudinal movement of current. Since the endothelial cells are extremely well coupled to each other, but do not themselves have many open ion channels, the current spreads effectively along this monolayer of cells. Overall the cross-talk between endothelial and smooth muscle cells favours endothelium-dependent dilation of arteries, and conduction of hyperpolarization to reduce vascular resistance and improve microvascular blood flow.