Differential effects of unaggregated and aggregated amyloid beta protein (1-40) on K(+) channel currents in primary cultures of rat cerebellar granule and cortical neurones.
The effects of amyloid beta protein on voltage-gated K(+) channel currents were studied using the whole-cell patch-clamp technique. The 1-40 amino acid form of amyloid beta protein was applied to primary cultures of rat cerebellar granule and cortical neurones for 24 h. Both the unaggregated and aggregated forms of the peptide, which have differing biological activities, were used. In cerebellar granule neurones, 24-h pre-incubation with 1 microM unaggregated amyloid beta protein resulted in a 60% increase in the 'A'-type component of K(+) current. Increased delayed rectifier activity was Cd(2+)-sensitive and was presumed to be secondary to an increase in voltage-gated Ca(2+) channel current activity. Unaggregated amyloid beta protein had no effect on any component of the K(+) channel current in cortical neurones. One micromolar of aggregated amyloid beta protein had no effect on K(+) channel current in either cell type but reduced cell survival within 24 h as measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays. The unaggregated form of amyloid beta protein had no neurotoxic effects when applied to either neurone type for up to 72 h. These data indicate that the unaggregated, non-pathological form of amyloid beta protein causes changes in the ion channel function of neurones, possibly reflecting a physiological role for the peptide.
Ramsden
M
M
School of Biomedical Sciences, University of Leeds, Leeds, UK.
Plant
L D
LD
Webster
N J
NJ
Vaughan
P F
PF
Henderson
Z
Z
Pearson
H A
HA
D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D012995:Solubility
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D015221:Potassium Channels; C078592:amyloid beta-protein (1-40); D019256:Cadmium Chloride; D011188:Potassium