Third pathway: Endothelium-dependent hyperpolarization

Abstract

The mechanism of endothelium-dependent hyperpolarizations, once attributed to an elusive endothelium-derived hyperpolarizing factor (EDHF), is better understood. The first steps involve an increase in the intracellular calcium concentration of the endothelial cells followed by the opening of endothelial calcium-activated potassium channels and the hyperpolarization of the endothelial cells. In certain arteries, these endothelial events are under the control of the endothelial cytochrome P450 monooxygenase. Then, the endothelium-dependent hyperpolarization of the smooth muscle cells can be evoked by direct electrical coupling through myo-endothelial junctions, accumulation of potassium ions in the intracellular space between the endothelial and the smooth muscle cells, and in rare occasions the release of a metabolite(s) of arachidonic acid via the cytochrome P450 pathway. These various mechanisms are not necessarily exclusive and can occur simultaneously and even in synergy. © 2003 Wiley-Liss, Inc.