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.
Kerrigan
Talitha L
TL
Institutes of aMembrane and Systems Biology bCardiovascular Research, University of Leeds, Leeds, UK.
Atkinson
Lucy
L
Peers
Chris
C
Pearson
Hugh A
HA
D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D051672:Shal Potassium Channels / Q000235:genetics / Q000502:physiology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051672:Shal Potassium Channels; C078592:amyloid beta-protein (1-40); D011188:Potassium