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 Ca 2+ concentrations ([Ca 2+ ] i ) was explored by using the Ca 2+ -sensitive probe fura-2. Maprotiline at concentrations greater than 100 μM caused a rapid rise in [Ca 2+ ] i in a concentration-dependent manner (EC 50 = 200 μM). Maprotiline-induced [Ca 2+ ] i rise was reduced by 50% by removal of extracellular Ca 2+ . Maprotiline-induced [Ca 2+ ] 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 Ca 2+ -ATPase, caused a monophasic [Ca 2+ ] 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 [Ca 2+ ] i rises. These findings suggest that in human neuroblastoma cells, maprotiline increases [Ca 2+ ] i by stimulating extracellular Ca 2+ influx and also by causing intracellular Ca 2+ release from the endoplasmic reticulum via a phospholiase C-independent manner.