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 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.
Willmott
N J
NJ
St. Bartholomew's and the Royal London School of Medicine and Dentistry (Queen Mary and Westfield College), Department of Pharmacology, UK.
Choudhury
Q
Q
Flower
R J
RJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D006801:Humans; D008345:Manganese / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D009636:Norbornanes; D019284:Thapsigargin / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology
D001952:Bridged-Ring Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D004546:Elapid Venoms; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C067971:calciseptine; D008345:Manganese; D004533:Egtazic Acid; C046498:tricyclodecane-9-yl-xanthogenate; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D009529:Nicardipine; D002118:Calcium