Abnormal function of potassium channels in platelets of patients with Alzheimer's disease.
BACKGROUND
Reports of abnormalities of potassium-channel function in various cultured cells of Alzheimer's disease patients led us to attempt to characterise the pharmacological characteristics of the abnormal channel.


METHODS
We studied platelets from 14 patients with Alzheimer-type dementia and 14 non-demented controls matched for age and sex. The effects of specific inhibitors of K+ channels on the efflux of rubidium-86 ions, a radioactive analogue of K+, from the platelets were measured.


RESULTS
Normal platelets contain three types of K+ channel, sensitive to the inhibitory actions of apamin (small-conductance calcium-dependent potassium channels), charybdotoxin (of less specificity, but probably intermediate-conductance calcium-dependent K+ channels), and alpha-dendrotoxin (voltage-sensitive K+ channels). However, 8Rb+ efflux from the platelets of patients with Alzheimer-type dementia was not inhibited by either apamin or charybdotoxin. By contrast, inhibition by alpha-dendrotoxin did occur.


CONCLUSIONS
Our results suggest that calcium-dependent K+ channels in platelets are selectively impaired in Alzheimer's disease. A similar abnormality in neurons could contribute to the pathophysiology of the disorder.
de Silva
H A
HA
University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Aronson
J K
JK
Grahame-Smith
D G
DG
Jobst
K A
KA
Smith
A D
AD
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000503:physiopathology; D000704:Analysis of Variance; D001030:Apamin / Q000494:pharmacology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology*; D004347:Drug Interactions; D004546:Elapid Venoms / Q000494:pharmacology*; D005260:Female; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
D004546:Elapid Venoms; D006490:Hemostatics; D007476:Ionophores; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; D015759:Ionomycin; C020273:dendrotoxin; D013917:Thrombin; D012413:Rubidium