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

The Alzheimer's disease related peptide annyloid 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 cells expressing Kv4.2 subunits, whole-cell patch clamp of K+ currents revealed that preincubation of cells with recombinant human or rat A beta(1-40) (10nM for 24h) 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.