LP-805, a releaser of endothelium-derived nitric oxide, activates an endothelial calcium permeable non-specific cation channel
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The actions of LP-805, a releaser of endothelium-derived nitric oxide, on Ca2+ permeable non-specific cation channel in cultured bovine pulmonary artery endothelial cells (BPAECs) were investigated using patch-clamp technique. In Ca2+ saline bath solution, 10 microM LP-805 increased inward and outward currents. LP-805 evoked currents were reversibly blocked by 50 microM La3+, an inorganic Ca2+ influx blocker. In Ca2+ and Na+ free saline bath solution, 10 microM LP-805 did not evoke these currents, when 2 mM Ca2+ was then added to the bath the inward current increased. Furthermore, in the Na+ saline bath solution (Ca2+ free), 10 microM LP-805 increased similar inward and outward currents, which were blocked by 50 microM La3+. LP-805 evoked currents were carried by either Ca2+ or Na+. With the pipette solution containing 11 mM EGTA, 10 microM LP-805 activated the inward and outward currents. The increase of inward and outward currents by 10 microM LP-805 was inhibited by 1 mM Ni2+ but not by 1 microM nicardipine or 50 microM SKF 96365. In conclusion, LP-805 increases Ca2+ influx into vascular endothelial cells through Ca2+ permeable non-specific cation channels. This may explain the release of endothelium-derived nitric oxide in endothelial cells by LP-805.
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