Figure 4.

Endothelial K_IR channels: Amplifiers and sensors of extracellular K⁺. Hyperpolarization of endothelial cells, due to Ca²⁺-dependent activation of endothelial cell IK_Ca and SK_Ca, or by activation of other endothelial cell K⁺ channels such as ATP-dependent K⁺ channels (K_ATP) can activate endothelial cell K_IR channels, amplifying the initial hyperpolarization in a positive feed-back manner. Conduction of this hyperpolarization to adjacent endothelial cells that are electrically coupled by gap junctions, can also recruit K_IR channels amplifying the hyperpolarization and promoting conduction of this electrical signal. Membrane hyperpolarization may promote Ca²⁺ entry into the endothelial cells through store-operated channels, although this is controversial. The resulting endothelial cell hyperpolarization can then be conducted, through myoendothelial gap junctions, to overlying smooth muscle cells, deactivating smooth muscle voltage-gated Ca²⁺ channels, reducing intracellular Ca²⁺ and promoting vasodilatation. Endothelial cell K⁺ channels also can be recruited by elevation of extracellular K⁺ concentration in their microenvironment by adjacent endothelial cell or smooth muscle cell K⁺ channels. This mechanism may allow endothelium-derived vasodilators, such as NO, prostacyclin (PGI₂) or epoxides of arachidonic acid (EETs), which act, in part, by activating smooth muscle K⁺ channels, to utilize endothelial cell K_IR channels in their mechanism of action. See text for more information. Figure redrawn and adapted from [56], with permission.