CA2-NITROSYLATION( POOL EMPTYING STIMULATES CA2+ ENTRY ACTIVATED BY S)

The entry of Ca2+ following Ca2+ pool release is a major component of Ca2+ signals; yet despite intense study, how ''store-operated'' entry channels are activated is unresolved. Because S-nitrosylation has beco me recognized as an important regulatory modification of several key c hannel proteins, its role in Ca2+ entry was investigated. A novel clas s of lipophilic NO donors activated Ca2+ entry independent of the well defined NO target, guanylate cyclase. Strikingly similar entry of Ca2 + induced by cell permeant alkylators indicated that this Ca2+ entry p rocess was activated through thiol modification Significantly, Ca2+ en try activated by either NO donors or alkylators was highly stimulated by Ca2+ pool depletion, which increased both the rate of Ca2+ release and the sensitivity to thiol modifiers. The results indicate that S-ni trosylation underlies activation of an important store-operated Ca2+ e ntry mechanism.