Differentiation of the human monocytic cell line U937 results in an upregulation of the calcium release‐activated current, ICRAC.

1. Single cell fura‐2 fluorescence measurements and whole‐cell patch clamp recordings were used to investigate the effects of macrophage‐like differentiation, induced by dibutyryl cAMP (dbcAMP), on Ca2+ influx triggered by Ca2+ store depletion in the human monocytic cell line, U937. 2. In differentiated cells, the rise in intracellular [Ca2+] following store depletion by thapsigargin (TG) in nominally Ca(2+)‐free solution was 94% greater and the [Ca2+]i rise on subsequent re‐addition of external Ca2+ (2 mM) was 292% greater than in undifferentiated cells. 3. Under conditions where [Ca2+]i was buffered by BAPTA, TG‐induced store depletion failed to activate a detectable inward Ca2+ current in undifferentiated U937 cells. Under identical conditions, store depletion of differentiated U937 cells generated an inwardly rectifying Ca(2+)‐selective current which showed no reversal from ‐140 to +30 mV and was blocked by 1 microM external La3+; characteristics of the calcium release‐activated Ca2+ current (ICRAC) identified in other cells. 4. We conclude that U937 cells show a differentiation‐dependent upregulation of a store‐mediated Ca2+ entry pathway, identified as ICRAC, which is not correlated with the small associated increase in the size of TG‐sensitive Ca2+ pools.