Identification of functional type 1 ryanodine receptors in mouse dendritic cells.
Ca(2+) signaling plays an important role in the function of dendritic cells (DC), the specialized antigen-presenting cells of the immune system. Here we describe functional ryanodine receptor (RyR) Ca(2+) release channels in murine, bone marrow-derived DC. RT-PCR analysis identified selective expression of the type 1 RyR, with higher levels detected in immature rather than mature DC. The RyR activators caffeine, FK506, ryanodine and 4-chloro-m-cresol mobilized Ca(2+) in DC, and responses to 4-chloro-m-cresol were inhibited by dantrolene. Furthermore, activation of RyRs both inhibited subsequent inositol trisphosphate-mediated Ca(2+) release and provoked store-operated Ca(2+) entry, suggesting a functional interaction between these intracellular Ca(2+) channels. Thus, the RyR1 channel may play an intrinsic role in Ca(2+) signaling in DC.
O'Connell
Peta J
PJ
The John P. Roberts Research Institute, London, Canada.
Klyachko
Vitaly A
VA
Ahern
Gerard P
GP
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D003713:Dendritic Cells / Q000737:chemistry / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000302:isolation & purification / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D016559:Tacrolimus