The phosphoinositide 3 kinase (PI3K) plays a pivotal role in the regulation of dendritic cells (DCs), antigen-presenting cells that are able to initiate primary immune responses and to establish immunological memory. PI3K is an endogenous suppressor of interleukin 12 (IL-12) production in DCs that is triggered by Toll- like receptor signaling. Inhibition of IL-12 production limits Th1 polarization. On the other hand, PI3K is an important regulator of various ion channels. The present study aimed to explore whether ion channels in DCs are regulated by PI3K and whether they are important for DC function. To this end, DCs were isolated from murine bone marrow and ion channel activity was determined by patch clamp. As a result, DCs express voltage-gated K+ channels (Kv), which are blocked by Stichodactyla helianthus toxin (ShK, 2.5 nM). A significant upregulation of Kv currents was observed upon maturation of DCs as induced by stimulation of the cells with lipopolysaccharide (LPS, 0.1 mg/ml, 48 h). A dramatic increase of Kv current amplitude was observed following preincubation of the cells with LY294002 (100 nM), a specific inhibitor of PI3K. Inhibition by LY294002 was followed by a significant increase of IL-12 production. The stimulation of IL-12 release by LPS was significantly blunted by ShK. The observations point to a role of PI3K-dependent Kv channels in the regulation of DC function.