Dendritic cells (DCs) are antigen-presenting cells that play a pivotal role in the regulation of immune responses. Mouse bone marrow-derived DCs express voltage-gated K⁺ (Kv) channels, which are upregulated upon LPS-induced DC maturation and contribute to the regulation of Ca²⁺ entry, cytokine release, migration, phagocytosis and MHC class II expression. The Kv channels in DCs are suppressed by the phosphoinositide 3 (PI3) kinase. PI3 kinase-dependent signaling involves activation of protein kinase B (PKB/Akt)/serum- and glucocorticoid inducible kinase (SGK) isoforms, which in turn phosphorylate and inhibit the glycogen synthase kinase GSK3. The present study explored, whether PI3 kinase-dependent GSK3 regulation participates in the regulation of Kv channels in DCs. To this end, Kv channel activity was determined by patch clamp in DCs isolated from murine bone marrow of gene targeted knockin mice carrying mutated and thus PKB/SGK-resistant GSK3a,ß (gsk3^KI) and of their wild type littermates (gsk3^WT). As a result, Western blot revealed GSK3 phosphorylation in DCs, which was reversed by preincubation of the cells with the PI3 kinase inhibitor wortmannin (100 nM). Kv currents were higher in gsk3^KI than in gsk3^WT DCs. Preincubation of the cells with wortmannin (100 nM, 2h) significantly increased Kv currents in DCs from gsk3^WT mice but not in DCs from gsk3^KI mice. In conclusion, PI3 kinase-dependent regulation of Kv channels in DCs involves phosphorylation of GSK3.