Ca2+ entry mediated by store depletion, S-nitrosylation, and TRP3 channels

Damian B. Van Rossum, Randen L. Patterson, Hong Tao Ma, Donald L. Gill

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


The mechanism for coupling between Ca2+ stores and store-operated channels (SOCs) is an important but unresolved question. SOC-mediated Ca2+ entry is complex and may reflect more than one type of channel and coupling mechanism. To assess such possible divergence the function and coupling of SOCs was compared with two other distinct yet related Ca2+ entry mechanisms. SOC coupling in DDT1MF-2 smooth muscle cells was prevented by the permeant inositol 1,4,5-trisphosphate (InsP3) receptor blockers, 2-aminoethoxydiphenyl borate (2-APB) and xestospongin C. In contrast, Ca2+ entry induced by S-nitrosylation and potentiated by store depletion (Ma, H.-T., Favre, C. J., Patterson, R. L., Stone, M. R., and Gill, D. L. (1999) J. Biol. Chem. 274, 35318-35324) was unaffected by 2-APB, suggesting that this entry mechanism is independent of InsP3 receptors. The cycloalkyl lactamimide, MDL-12,330A (MDL), prevented SOC activation (IC(50) 10 μM) and similarly completely blocked S-nitrosylation-mediated Ca2+ entry. Ca2+ entry mediated by the TRP3 channel stably expressed in HEK293 cells was activated by phospholipase C-coupled receptors but independent of Ca2+ store depletion (Ma, H.-T., Patterson, R. L., van Rossum, D. B., Birnbaumer, L., Hikoshiba, K., and Gill, D. L. (2000) Science 287, 1647-1651). Receptor-induced TRP3 activation was 2-APB-sensitive and fully blocked by MDL. Direct stimulation of TRP3 channels by the permeant diacylglycerol derivative, 1-oleoyl-2-acetyl-sn-glycerol, was not blocked by 2-APB, but was again prevented by MDL. The results indicate that although the activation and coupling processes for each of the three entry mechanisms are distinct, sensitivity to MDL is a feature shared by all three mechanisms, suggesting there may be a common structural feature in the channels themselves or an associated regulatory component.

Original languageEnglish (US)
Pages (from-to)28562-28568
Number of pages7
JournalJournal of Biological Chemistry
Issue number37
StatePublished - Sep 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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