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

The Alzheimer's disease related peptide amyloid beta (Abeta) might have a physiological role in upregulating K channel currents in neurones. Earlier studies used the human form of Abeta1-40 on rat neurones. We sought to confirm our hypothesis by use of rat Abeta, 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 Abeta1-40 (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 Abeta are effective in modulating K currents. The effectiveness of nonaggregating rat Abeta also strongly supports a physiological role for the peptide.