Fundamental Ca2+ signaling mechanisms in mouse dendritic cells: CRAC is the major Ca2+ entry pathway

Shyue Fang Hsu, Peta J. O'Connell, Vitaly A. Klyachko, Michael N. Badminton, Angus W. Thomson, Meyer B. Jackson, David E. Clapham, Gerard P. Ahern

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Although Ca2+-signaling processes are thought to underlie many dendritic cell (DC) functions, the Ca2+ entry pathways are unknown. Therefore, we investigated Ca2+-signaling in mouse myeloid DC using Ca2+ imaging and electrophysiological techniques. Neither Ca2+ currents nor changes in intracellular Ca2+ were detected following membrane depolarization, ruling out the presence of functional voltage-dependent Ca2+ channels. ATP, a purinergic receptor ligand, and 1-4 dihydropyridines, previously suggested to activate a plasma membrane Ca2+ channel in human myeloid DC, both elicited Ca2+ rises in murine DC. However, in this study these responses were found to be due to mobilization from intracellular stores rather than by Ca2+ entry. In contrast, Ca2+ influx was activated by depletion of intracellular Ca2+ stores with thapsigargin, or inositoi trisphosphate. This Ca2+ influx was enhanced by membrane hyperpolarization, inhibited by SKF 96365, and exhibited a cation permeability similar to the Ca2+ release-activated Ca2+ channel (CRAC) found in T lymphocytes. Furthermore, ATP, a putative DC chemotactic and maturation factor, induced a delayed Ca2+ entry with a voltage dependence similar to CRAC. Moreover, the level of phenotypic DC maturation was correlated with the extracellular Ca2+ concentration and enhanced by thapsigargin treatment. These results suggest that CRAC is a major pathway for Ca2+ entry in mouse myeloid DC and support the proposal that CRAC participates in DC maturation and migration.

Original languageEnglish
Pages (from-to)6126-6133
Number of pages8
JournalJournal of Immunology
Issue number10
StatePublished - May 15 2001


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