EMS transmission mechanisms. (A) Comparison of the vascular volume in a 1 mm³ block of cortical tissue comprised by surface arteries, penetrating arterioles, and the capillary bed. Capillaries comprise about 85% of the vasculature by volume, with the penetrating arterioles contributing just 3%. Thus, the capillaries are ideally positioned to act as a sensory array communicating information on tissue activity to the arterioles to regulate blood flow. Adapted with permission from Gould et al. (2017). (B) The central image depicts an arteriole lined by arterial endothelial cells (aECs) and surrounded by smooth muscle cells (SMCs). Downstream of this emerge capillaries, the proximal branches of which are covered in contractile pericytes. Deeper downstream branches are covered by thin-strand pericytes. The dotted box depicts events leading to the initiation of EMS in the capillary bed, leading to the generation and transmission of hyperpolarizing signals. In inset i (middle), a specific example is given for a decrease in glucose availability based on Hariharan et al. (2022), which engages K_ATP channels. This hyperpolarization can be passed via gap junctions (GJs) into the underlying capillary endothelial cells (cECs), which may then transmit the signal upstream via the mechanism depicted in inset ii (bottom). Here, hyperpolarization in the endothelium relieves the voltage-dependent block of Kir2.1 channels by polyamines, leading to K⁺ efflux and regeneration of membrane hyperpolarization through the engagement of further Kir2.1 channels as the signal travels upstream. Once it arrives in the proximal capillaries and arteriolar segment (inset iii, top), the electrical signal can be transmitted via gap junctions into both the contractile pericytes and upstream SMCs, where its arrival decreases the open probability of voltage-dependent Ca²⁺ channels and produces a decrease in intracellular Ca²⁺ which relaxes the Ca²⁺-sensitive contractile machinery and promotes vasodilation and an increase in blood flow.