Ryanodine receptor (RyR) is a Ca2+ channel that mediates Ca2+ release from intracellular stores. Altered Ca2+ homeostasis in skeletal muscle which usually occurs as a result of point mutations in type I RyR1 (RyR1) is a key molecular event triggering malignant hyperthermia (MH). There are three RyR isoforms, and we herein show, for the first time, that human dendritic cells (DCs) preferentially express RyR1 mRNA among them. The RyR activator, 4-chloro-m-cresol (4CmC), induced Ca2+ release in DCs, and this response was eliminated by dantrolene, an inhibitor of the RyR I, and was unaffected by xestospongin Q a selective inhibitor Of IP3 receptor. Activation of RyR1 reduced LPS-induced IL-10 production, promoted the expression of HLA-DR and CD86, and thereby exhibited an improved capacity to stimulate allogeneic T cells. These findings demonstrate that RyR1-mediated calcium signaling modifies diverse DC responses and suggest the feasibility of using DC preparations for the diagnosis of MH. (c) 2007 Elsevier Inc. All rights reserved.