We have previously shown that the Alzheimer’s disease related peptide amyloid beta protein (Aβ) can increase expression of the ‘A’-type K⁺ channel current in rat cerebellar granule neurones (Ramsden et al. 2001). This effect was a property of the soluble form of the peptide and could not be observed following Aβ aggregation. These earlier studies used a synthetic, human form of Aβ_1-40; however, the endogenous, rat Aβ differs from human by 3 amino acids. In this study we have investigated the effects of recombinant human Aβ and compared it to the effect of Aβ with a rodent sequence. Dissociated cultures of cerebellar granule neurones were prepared from 6-8 day old rats and maintained as reported previously (Ramsden et al. 2001). In separate experiments, a HEK293 cell line stably overexpressing recombinant rat Kv4.2 was used. Whole-cell patch clamp measurements of K⁺ channel currents were carried out using quasi-physiological intra- and extracellular solutions as before (Ramsden et al. 2001). Stock Aβ was dissolved in DMSO before dilution in culture media to a concentration of 10nM and applied to cultures for 24 hours. Statistical differences were assessed using repeated measures ANOVA with Tukey’s post-hoc test or a paired Student’s t test as appropriate. Human recombinant Aβ_1-40 caused a large (1.5-fold) increase in the peak K⁺ channel current density/voltage (I-V) relationship in cerebellar granule neurones (n=17 controls, 17 Aβ-treated cells, repeated measures ANOVA, p < 0.05). At a test potential of +50mV, current increased from 0.77 ± 0.16 nA/pF to 1.15 ± 0.16 nA/pF. Similarly, treatment with synthetic rat Aβ_1-40 increased the I-V by 2-fold from 0.71 ± 0.14 nA/pF to 1.45 ± 0.19 nA/pF at +50mV (n=19 control, 19 Aβ-treated cells, repeated measures ANOVA, p < 0.05). The inactivating, ‘A’-type, component of the K⁺ current I-V was particularly sensitive to the effects of synthetic rat Aβ_1-40 (3.4-fold increase, n=19 control, 19 treated cells, repeated measures ANOVA, p < 0.05) and of human recombinant Aβ_1-40 (2.6-fold increase, n=17 control, 17 treated cells, repeated measures ANOVA, p < 0.05). The selective Kv 4.2 subunit blocker heteropodatoxin (75nM) was applied to investigate the effects of Aβ_1-40 on the Kv 4.2 subunit. In control experiments HEK 293 cells stably transfected with the Kv 4.2 subunit underwent substantial block of K⁺ channel current. Mean current density at +50mV prior to application of the blocker was 1.8 ± 0.03 nA/pF whereas current after application of the blocker was 0.08 ± 0.02 nA/pF (n=3, Student’s paired t test, p <0.05). These data indicate that Aβ_1-40 produced using recombinant technology has the same effect on K⁺ channel expression as Aβ synthesised using chemical means. Furthermore, rodent and human forms of Aβ are equally effective in their ability to modulate K⁺ channel currents.