Figure 1.

Diffusible and contact-mediated mechanisms of endothelium-dependent smooth muscle hyperpolarization. In certain vascular beds in specific conditions, diffusible factors such as epoxyeicosatrienoic acids (EETs), K⁺ ions, and hydrogen peroxide (H₂O₂) hyperpolarize smooth muscle cells through the opening of potassium channels and/or Na⁺/K⁺-ATPase. In addition, endothelium-dependent hyperpolarization initiated in endothelial cells with a rise in intracellular calcium and the subsequent activation of small (SK_Ca) and intermediate conductance (IK_Ca) Ca²⁺-activated K⁺ channels spreads to adjacent smooth muscle cells via myoendothelial gap junctions (MEGJs) in a number of vascular beds. In some vascular beds, combination of diffusible and contact-mediated mechanisms underpin smooth muscle hyperpolarization.