Effect of maprotiline on Ca²⁺ movement in human neuroblastoma cells

In human neuroblastoma IMR32 cells, the effect of the anti-depressant maprotiline on baseline intracellular Ca²⁺ concentrations ([Ca ²⁺]_i) was explored by using the Ca²⁺-sensitive probe fura-2. Maprotiline at concentrations greater than 100 μM caused a rapid rise in [Ca²⁺]_i in a concentration-dependent manner (EC₅₀ = 200 μM). Maprotiline-induced [Ca²⁺]_i rise was reduced by 50% by removal of extracellular Ca²⁺. Maprotiline-induced [Ca²⁺]_i rises were inhibited by half by nifedipine, but was unaffected by verapamil or diiltiazem. In Ca ²⁺-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺-ATPase, caused a monophasic [Ca²⁺] _i rise, after which the increasing effect of maprotiline on [Ca ²⁺]_i was abolished. U73122, an inhibitor of phospholipase C, did not affect maprotiline-induced [Ca²⁺]_i rises. These findings suggest that in human neuroblastoma cells, maprotiline increases [Ca²⁺]_i by stimulating extracellular Ca²⁺ influx and also by causing intracellular Ca²⁺ release from the endoplasmic reticulum via a phospholiase C-independent manner.