Amyloid peptides have previously been shown to trigger apoptosis of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. The apoptosis is mediated by stimulation of acid sphingomyelinase with subsequent formation of ceramide. In other cell types ceramide is known to inhibit voltage gated K⁺ (Kv) channels, which are expressed in DCs and participate in the regulation of DC function. The present study explored whether amyloid peptides and/or ceramide modify the activity of Kv channels in DCs. To this end Kv channel activity was determined utilizing whole cell patch clamp in mouse bone marrow derived DCs from gene targeted mice lacking functional sphingomyelinase (asm^-/-) and age and gender matched wild type mice (asm^+/+). The DCs were exposed to 2 mM amyloid b-peptide (Ab_1-42) or to 10 mM C₂-ceramide. Exposure to Ab_1-42 resulted in ceramide formation and significant transient increase (within 1 hour) followed by significant decrease (within 12 hours) of Kv channel activity in asm^+/+ DCs but not in asm^-/- DCs. Ceramide exposure transiently increased (within 1 hour) and then significantly decreased (within 12 hours) Kv channel activity in both, asm^+/+ DCs and asm^-/- DCs. In conclusion, Ab_1-42 modifies voltage gated K⁺ channel activity in DCs through acid sphingomyelinase dependent formation of ceramide.