title: Different mechanisms can activate Ca2+ entrance via cation currents in endothelial cells.
abstract: Effects of Endothelin-1 (ET-1) and cyclopiazonic acid (CPA) on non-specific cation channels in cultured bovine pulmonary artery endothelial cells (BPAECs) were investigated using the patch-clamp technique. In a bath solution containing Ca2+ as a permeant cation, 10 nM ET-1 increased inward and outward currents and this current reversed at -10 mV instead of -60 mV. Under similar conditions, 10 microM CPA, an inhibitor of Ca2+ pumps in the sarcoplasmic reticulum, also increased both currents which now reversed near -10 mV. An inorganic Ca2+ influx blocker, La3+ at 50 microM completely blocked ET-1 and CPA-evoked currents restoring the reversal potential to -60 mV. ET-1 and CPA evoked currents were partially blocked by 50 microM SK&F 96365 (a putative inhibitor of receptor-mediated Ca2+ entry). ET-1 and CPA increased Ca2+ influx by activation of the Ca(2+)-permeable non-specific cation channels, which are gated by the depletion of intracellular Ca2+ stores in endothelial cells. These results, together with a previous study demonstrating that this Ca2+ entrance pathway can be opened directly by one vasodilator (LP-805) reveal that different mechanisms exist to activate Ca2+ entrance into endothelial cells. All may allow sustained release of endothelium-derived relaxing factor (EDRF).
authors: Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: M
authors: M
authors: Inazu
authors: H
authors: H
authors: Zhang
authors: E E
authors: EE
authors: Daniel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D016232:Endothelins; D007211:Indoles; D007811:Lanthanum; D002118:Calcium; C000543:cyclopiazonic acid