FUNCTIONAL IMPORTANCE OF THE DIHYDROPYRIDINE-SENSITIVE, YET VOLTAGE-INSENSITIVE STORE-OPERATED CA2+ INFLUX OF U937 CELLS

The Ca2+ current activated by Ca2+ store depletion in non-excitable ce lls is classically regarded as being dihydropyridine-insensitive, sugg esting that store-operated Ca2+ channels (SOCs) are dissimilar to volt age-gated Gate channels (VGCs) of excitable-cells. Here, we demonstrat e dihydropyridine-sensitivity for the store-operated Ca2+ influx induc ed by ATP and thapsigargin (Ig) in the non-excitable U937 cell-line, C a2+ store depletion by prior treatment of cells with either Tg or ATP, stimulated a Ca2+ entry mechanism that was inhibited by nicardipine, nifedipine, and the specific L-type Ca2+ channel blocker, calciseptine , A functional requirement for this Ca2+ influx mechanism in agonist-i nduced mitogenesis seemed likely, a since nicardipine, a particularly potent inhibitor of store-operated Ca2+ influx in these cells, suppres sed ATP- and Tg-stimulated cell proliferation, Depolarisation of cells with KCl, or gramicidin failed to elicit an increase in cytosolic Ca2 +, suggesting that while the store-operated Ca2+ influx channel of U93 7 cells shares pharmacologic properties with the L-type Ca2+ channel, it is voltage-insensitive and therefore may resemble an L-type Ca2+ ch annel lacking a voltage sensor.