Ca(2+) entry activated by S-nitrosylation. Relationship to store-operated ca(2+) entry.
The coupling between Ca(2+) pools and store-operated Ca(2+) entry channels (SOCs) remains an unresolved question. Recently, we revealed that Ca(2+) entry could be activated in response to S-nitrosylation and that this process was stimulated by Ca(2+) 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(1)MF-2 smooth muscle cells and DC-3F fibroblasts, Ca(2+) 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 Ca(2+) removal, closely resembling activation of SOC activity in the same cells. The nonadditivity of SOC and NO donor-activated Ca(2+) entry suggested a single entry mechanism. Calyculin A-induced reorganization of the actin cytoskeleton prevented SOC but had no effect on GEA3162-induced Ca(2+) 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 Ba(2+) entry and sensitivity to blockade by La(3+) 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 Ca(2+) entry.
Ma
H T
HT
Department of Biochemistry, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Favre
C J
CJ
Patterson
R L
RL
Stone
M R
MR
Gill
D L
DL
D000818:Animals; D001464:Barium / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D005033:Ethylmaleimide / Q000494:pharmacology; D007700:Kinetics; D009130:Muscle, Smooth; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology*
D015220:Calcium Channels; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D001464:Barium; D019284:Thapsigargin; C082874:GEA 3162; D005033:Ethylmaleimide; D002118:Calcium