Control of neuronal spiking patterns resides, in part, in the type and degree of expression of voltage-gated K⁺ channel subunits. Previous studies have revealed that soluble forms of the Alzheimer's disease associated amyloid β protein (Aβ) can increase the ‘A’-type current in neurones. In this study, we define the molecular basis for this increase and show that endogenous production of Aβ is important in the modulation of Kv4.2 and Kv4.3 subunit expression in central neurones. A-type K⁺ currents, and Kv4.2 and Kv4.3 subunit expression, were transiently increased in cerebellar granule neurones by the 1–40 and 1–42 forms of Aβ (100nM, 2–24h). Currents through recombinant Kv4.2 channels expressed in HEK293 cells were increased in a similar fashion to those through the native channels. Increases in ‘A’-type current could be prevented by the use of cycloheximide and brefeldin A, indicating that protein expression and trafficking processes were altered by Aβ, rather than protein degredation. Endogenous Aβ production in cerebellar granule neurones was blocked using inhibitors of either γ- or β-secretase and resulted in decreased K⁺ current. Crucially this could be prevented by co-application of exogenous Aβ (1nM), however, no change in Kv4.2 or Kv4.3 subunit expression occurred. These data show that Aβ is a modulator of Kv4 subunit expression in neurones at both the functional and the molecular level. Thus Aβ is not only involved in Alzheimer pathology, but is also an important physiological regulator of ion channel expression and hence neuronal excitability.