Aims: Dendritic cells (DCs) are powerful antigen-presenting cells that are critical for the initiation and regulation of adaptive immunity and for the maintenance of both central and peripheral tolerance. Voltage-gated K⁺ channels (Kv) have been recently shown to play a role in the regulation of cytokine production, maturation and migration of murine DCs. Amyloid peptides are formed during inflammation and modify the functions of immune cells. The purpose of this project was to study the effects of amyloid on Kv channel activity and functions of DCs. Methods: DCs were isolated from bone marrow of wild type and acid sphingomyelinase (Asm) knockout (asm^-/-) mice and incubated with amyloid b-peptide (Ab_1-42, 2 mM, 12 h) or C2-ceramide (10 mM, 12 h). Whole-cell patch clamp experiments were performed to measure Kv currents. Ceramide formation and Annexin V binding as a measure of phosphatidyl serine exposure on the outer leaflet of cell membrane were detected by flow cytometry. Results: Here we show that Ab_1-42 triggered ceramide formation and apoptosis in DCs obtained from wild type mice, but not in DCs from asm^-/- mice. In patch-clamp experiments, Ab_1-42 led to the suppression of Kv channel activity in wild type but not in asm^-/- DCs, whereas treatment of DCs with C2-ceramide impaired Kv channel activity in DCs from both genotypes. Conclusion: Ab_1-42 reduces Kv channel activity in DCs by Asm-dependent ceramide production, an effect that may contribute to Ab_1-42-mediated DC apoptosis.