Inhibition of a store‐operated Ca2+ entry pathway in human endothelial cells by the isoquinoline derivative LOE 908

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Abstract
The novel cation channel blocker, LOE 908, was tested for its effects on Ca2+ entry and membrane currents activated by depletion of intracellular Ca2+ stores in human endothelial cells. LOE 908 inhibited store‐operated Ca2+ entry induced by direct depletion of Ca2+ stores with 100 nM thapsigargin or 100 nM ionomycin with an EC50 of 2 μm and 4 μm, respectively. LOE 908 did not affect thapsigargin‐ or ionomycin‐induced Ca2+ release from intracellular stores up to concentrations of 3 μm. LOE 908 reversibly suppressed thapsigargin‐ as well as ionomycin‐induced whole‐cell membrane currents. The LOE 908‐sensitive membrane conductance corresponded to a cation permeability of 5.5 and 6.9 fold selectivity for Ca2+ over K+ in the presence of thapsigargin and ionomycin, respectively. Our results suggest that the isoquinoline, LOE 908 is a novel, potent inhibitor of the store‐operated (capacitive) Ca2+ entry pathway in endothelial cells.