Modulation of 'A'-type K+ current by rodent and human forms of amyloid [beta] protein

The Alzheimer's disease related peptide amyloid [beta] (A[beta]) might have a physiological role in upregulating K+ channel currents in neurones. Earlier studies used the human form of A[beta]1-40 on rat neurones. We sought to confirm our hypothesis by use of rat A[beta], which has no Alzheimer's association. In rat cerebellar granule neurones and HEK293 ceils expressing Kv4.2 submits, whole-cell patch clamp of K+ currents revealed that preincubation of cells with recombinant human or rat A[beta]1-40 (10 nM for 24 h) significantly increased K+ channel current density. This was accompanied by increased mRNA levels for Kv4.2. These data indicate that rodent and human A[beta] are effective in modulating K+ currents. The effectiveness of nonaggregating rat A[beta] also strongly supports a physiological role for the peptide.