Endothelium-dependent cerebral artery dilation mediated by transient receptor potential and Ca2+-activated K+ channels

Abstract

Intracellular Ca(2+) plays a dual role in the regulation of vascular tone. Smooth muscle cell Ca(2+) influx causes vasoconstriction, whereas transient localized Ca(2+) release from intracellular stores in either endothelial or vascular smooth muscle cells can elicit membrane hyperpolarization and vasodilation by stimulating Ca(2+)-activated K(+) (K(Ca)) channels. Recent evidence suggests that Ca(2+) influx via transient receptor potential (TRP) channels can cause arterial dilation by activating K(Ca) channels. Current findings in this area are summarized. Key features of the main KCa channels present in the vascular wall (K(Ca)1.1, K(Ca)2.3, and K(Ca)3.1) and TRP channels are briefly reviewed. Arterial dilation mediated by endothelial TRP channels sensitive to dietary molecules are reviewed. Recent reports demonstrate that 2 chemosensitive TRP channels, TRPA1 and TRPV3, are present in native cerebral artery endothelial cells. These channels are activated by substances found in foods such as garlic, mustard oil, and oregano and mediate K(Ca)-dependent endothelium-dependent vasodilation. The role of TRPV4 channels in mediating vasodilation in response to epoxyeicosatrienoic acids (EETs) is also reviewed. Stimulation of TRPV4 channels with 11,12-EET in cerebral artery smooth muscle cells causes membrane hyperpolarization and vasodilation by increasing the frequency of Ca(2+) release from intracellular stores, which in turn increases K(Ca)1.1 channel activity. Evidence that K(Ca)2.3 and K(Ca)3.1 channels in endothelial cells and K(Ca)1.1 channels in smooth muscle are involved in TRPV4-dependent 11,12-EET–induced dilation of mesenteric arteries is discussed. These examples show that Ca(2+) influx through TRP channels in endothelial or smooth muscle cells influences vascular tone by increasing K(Ca) channel activity.