d-609 and calciseptine

The Ca2+ current activated by Ca2+ store depletion in non-excitable cells is classically regarded as being dihydropyridine-insensitive, suggesting that store-operated Ca2+ channels (SOCs) are dissimilar to voltage-gated Ca2+ channels (VGCs) of excitable-cells. Here, we demonstrate dihydropyridine-sensitivity for the store-operated Ca2+ influx induced by ATP and thapsigargin (Tg) in the non-excitable U937 cell-line. Ca2+ 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-induced mitogenesis seemed likely, since nicardipine, a particularly potent inhibitor of store-operated Ca2+ influx in these cells, suppressed 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 U937 cells shares pharmacologic properties with the L-type Ca2+ channel, it is voltage-insensitive and therefore may resemble an L-type Ca2+ channel lacking a voltage sensor.

Topics: Adenosine Triphosphate; Bridged-Ring Compounds; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Cell Division; Cell Line; Dihydropyridines; Egtazic Acid; Elapid Venoms; Humans; Manganese; Monocytes; Nicardipine; Norbornanes; Thapsigargin; Thiocarbamates; Thiones