Small and intermediate conductance, calcium-sensitive potassium channels (SK_Ca and IK_Ca) are of pivotal importance in triggering endothelium-dependent, vascular myocyte hyperpolarisations. The pharmacological signature of this process, sometimes known as the EDHF (endothelium-derived hyperpolarising factor) response is its sensitivity to a mixture of apamin (SK_Ca blocker) + TRAM-34 (IK_Ca blocker). Measurements using K⁺-selective electrodes show that the [K⁺] in the microdomain known as the myoendothelial space rises by about 6mM during endothelial cell activation. Following endothelial hyperpolarisation, myocyte hyperpolarisation usually follows in one, or in a combination of two, ways. Endothelial cells can signal 'electrotonically' to myocytes through gap junctions located between myocytes and endothelial-cell end feet that project through holes in the vessel's internal elastic lamina. Alternatively (or additionally), the increase in [K⁺] in the myoendothelial space both removes the inwardly-rectifying block on myocyte K_IR2.1 channels and activates myocyte Type 2 and/or Type 3 Na⁺/K⁺ ATPases. The spatial arrangement of endothelial cell K_Ca channels is not identical. SK_Ca channels are located in caveolae and their activation preferentially removes K_IR rectifying blockade. IK_Ca channels are non-caveolar and preferentially linked to myocyte Na⁺/K⁺ATPase activation. In addition, IK_Ca channels can be activated by endothelial cell G protein-coupled receptors that are themselves activated by [Ca²⁺] changes in the myoendothelial space associated with endothelial cell end-feet projections. Speculatively, the Ca²⁺ for their activation derives from myocytic extrusion mechanisms activated following myocyte contractions and contributes to a hyperpolarising 'switch-off' signal to the excited myocyte.