IonChannelsandTheirFunctionalRoleinVascularEndothelium

Endothelial cells (EC) form a multifunctional signal-transducing surface that performs different tasks dependent on its localization in the vessel tree. Arterial EC provide a pathway for delivery of oxygen from blood to tissue. They modulate the tone of vascular smooth muscle cells, which in turn controls blood pressure and blood flow by adjusting the caliber of arteries and arterioles. In the microvascular bed, EC regulate the permeation of various metabolites, macromolecules and gases, as well as autocrine and paracrine factors and are involved in the regulation of cell nutrition. In all vessel types, EC are involved in blood coagulation, control of the transport between blood and tissue, movement of cells adhering to EC, wound healing, and angiogenesis. Other functions require an active response of EC to various signals of mechanical, chemical, or neuronal nature. This signal transduction is impaired during vessel disease (arteriosclerosis) and injury, inflammation, or hemodynamic disturbances (hypertension). The role of ion channels in the transduction of these signals into cellular responses is still a matter of debate and has received substantial attention only in the last few years. Our current knowledge is limited to effects of ion channels on fast endothelial responses, these channels being mainly essential for the regulation of Ca2+ signaling. Here we illustrated the negative feedback of cyclic nucleotides (CNG)-induced membrane depolarization on Ca2+ entry. Ca2+ entry via receptor-activated cation channels (RACC) and/or store-operated or capacitative (SOC) elevates [Ca2+]i and stimulates endothelial nitric oxide synthase (eNOS). The subsequent activation of soluble guanylate cyclase (sGC) increases cGMP. cGMP and cAMP [via agonist activation of G protein-coupled receptors (GPCRs), Gs, and adenylate cyclase (AC)] activate CNG and/or nonselective cation channels (HCN) channels, which induces membrane depolarization. This depolarization exerts a negative feedback on Ca2+ entry via RACC/SOC. In addition, a feedback inhibition of Ca2+ entry channels via activation of PKG has been described.

Contributor: Kosi Gramatikoff, PhD

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