Endothelial cell, Ca2+-activated K channels (SKCa and IKCa channels) generate hyperpolarization that passes to the adjacent vascular smooth muscle cells to cause vasodilation in small resistance arterioles. IKCa channels expressed within endothelial cell projections toward the SMCs are activated by spontaneous Ca2+ events (Ca2+ puffs/pulsars). TRPV4 channels also cluster within this microdomain and are selectively activated at low intravascular pressure resulting in activation of endothelial cell IKCa channels and vasodilation, reducing the myogenic tone that underpins tissue blood-flow autoregulation.