The coupling between Ca2+ pools and store-operated Ca2+ entry channels (SOCs) remains an unresolved question. Recently, we revealed that Ca2+ entry could be activated in response to S-nitrosylation and that this process was stimulated by Ca2+ pool emptying (Favre, C. J., Ufret-Vincenty, C. A., Stone, M. R., Ma, H-T., and Gill, D. L. (1998) J. Biol. Chem. 273, 30855-30858). In DDT1MF-2 smooth muscle cells and DC-3F fibroblasts, Ca2+ entry activated by the lipophilic NO donor, GEA3162 (5-amino-3-(3,4- dichlorophenyl)-1,2,3,4-oxatriazolium), or the alkylator, N-ethylmaleimide, was observed to be strongly activated by transient external Ca2+ removal, closely resembling activation of SOC activity in the same cells. The nonadditivity of SOC and NO donor-activated Ca2+ entry suggested a single entry mechanism. Calyculin A-induced reorganization of the actin cytoskeleton prevented SOC but had no effect on GEA3162-induced Ca2+ entry. However, a single entry mechanism could account for both SOC and NO donor-activated entry if the latter reflected direct modification of the entry channel by S- nitrosylation, bypassing the normal coupling process between channels and pools. Small differences between SOC and GEA3162-activated Ba2+ entry and sensitivity to blockade by La3+ were observed, and in HEK293 cells SOC activity was observed without a response to thiol modification. It is concluded that in some cells, S-nitrosylation modifies an entry mechanism closely related to SOC and/or part of the regulatory machinery for SOC- mediated Ca2+ entry.
ASJC Scopus subject areas