Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The release of dilator agents from vascular endothelial cells is modulated by changes in cytosolic Ca(2+) concentration ([Ca(2+)](i)). In this study, we demonstrate the presence of a Ca(2+)-permeable cation channel in inside-out membrane patches of endothelial cells isolated from small mesenteric arteries. The activity of the channel is increased by KT-5823, a highly selective inhibitor of protein kinase G (PKG), while it is decreased by direct application of active PKG. Application of KT-5823 induces Ca(2+) influx in the endothelial cells isolated from small mesenteric arteries, and it also causes endothelium-dependent relaxations in isolated small mesenteric arteries. KT-5823-induced relaxations in small mesenteric arteries are greatly reduced by 35 mM K(+) or 50 nM charybdotoxin + 50 nM apamin, suggesting that endothelium-derived hyperpolarizing factor (EDHF) is the participating dilator. The involvement of EDHF is further supported by experiments in which the relaxations of small mesenteric arteries are shown to be accompanied by membrane repolarization. These data strongly argue for a major role of a PKG-sensitive cation channel in modulating the release of EDHF from endothelial cells in rat small mesenteric arteries.

Original publication

DOI

10.1152/ajpheart.2001.280.3.H1272

Type

Journal article

Journal

Am J Physiol Heart Circ Physiol

Publication Date

03/2001

Volume

280

Pages

H1272 - H1277

Keywords

Acetylcholine, Alkaloids, Animals, Biological Factors, Calcium, Carbazoles, Cations, Cyclic GMP-Dependent Protein Kinases, Endothelium, Vascular, Enzyme Inhibitors, Indoles, Ion Channel Gating, Ion Channels, Male, Membrane Potentials, Mesenteric Arteries, Patch-Clamp Techniques, Phenylephrine, Rats, Rats, Sprague-Dawley, Vascular Resistance, Vasoconstrictor Agents, Vasodilation, Vasodilator Agents