Identification of functional type 1 ryanodine receptors in mouse dendritic cells

Ca²⁺ 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) Ca²⁺ 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 Ca²⁺ in DC, and responses to 4-chloro-m-cresol were inhibited by dantrolene. Furthermore, activation of RyRs both inhibited subsequent inositol trisphosphate-mediated Ca²⁺ release and provoked store-operated Ca²⁺ entry, suggesting a functional interaction between these intracellular Ca²⁺ channels. Thus, the RyR1 channel may play an intrinsic role in Ca²⁺ signaling in DC.