Ca2+ entry activated by S-nitrosylation - Relationship to store-operated Ca2+ entry

The coupling between Ca2+ pools and store-operated Ca2+ entry channels (SOC s) remains an unresolved question. Recently, we revealed that Ca2+ entry co uld be activated in response to S-nitrosylation and that this process was s timulated 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 DDT,MF-S smooth muscle cells and DC-3F fibroblasts, Ca2+ entry activate d by the lipophilic NO donor, GEA3162 (5-amino-3- (3,4-dichlorophenyl) 1,2, 3,4-oxatriazolium), or the alkylator, N-ethylnaleimide, was observed to be strongly activated by transient external Ca2+ removal, closely resembling a ctivation of SOC activity in the same cells. The nonadditivity of SOC and N O 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 co uld account for both SOC and NO donor-activated entry if the latter reflect ed direct modification of the entry channel by S-nitrosylation, bypassing t he normal coupling process between channels and pools. Small differences be tween SOC and GEA3162-activated Ba2+ entry and sensitivity to blockade by L a3+ were observed, and in HEK293 cells SOC activity was observed without a response to thiol modification. It is concluded that in some cells, S-nitro sylation modifies an entry mechanism closely related to SOC and/or part of the regulatory machinery for SOC-mediated Ca2+ entry.