The anti-anginal drug fendiline increases intracellular Ca²⁺ levels in MG63 human osteosarcoma cells

The effect of fendiline, an anti-anginal drug, on cytosolic free Ca²⁺ levels ([Ca²⁺]_i) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca²⁺ indicator. Fendiline at concentrations between 1 and 200 μM increased [Ca²⁺]_i in a concentration-dependent manner and the signal saturated at 100 μM. The Ca²⁺ signal was inhibited by 65 ± 5% by Ca²⁺ removal and by 38 ± 5% by 10 μM nifedipine, but was unchanged by 10 μM La³⁺ or verapamil. In Ca²⁺-free medium, pre-treatment with 1 μM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor) to deplete the endoplasmic reticulum Ca²⁺ store inhibited fendiline-induced intracellular Ca²⁺ release. The Ca²⁺ release induced by 50 μM fendiline appeared to be independent of IP₃ because the [Ca²⁺]_i increase was unaltered by inhibiting phospholipase C with 2 μM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in [Ca²⁺]_i by inducing Ca²⁺ influx and Ca²⁺ release in an IP₃-independent manner.