Abnormal function of potassium channels in platelets of patients with Alzheimer's disease

• Published in: The Lancet (British edition) Vol. 352; no. 9140; pp. 1590 - 1593
• Main Authors: de Silva, H Asita, Aronson, Jeffrey K, Grahame-Smith, David G, Jobst, Kim A, Smith, A David
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 14.11.1998; Lancet; Elsevier Limited
• Subjects: Aged; Alzheimer Disease - blood; Alzheimer Disease - physiopathology; Alzheimer's disease; Analysis of Variance; Apamin - pharmacology; Biochemistry; Biological and medical sciences; Calcium; Case-Control Studies; Cells, Cultured; Charybdotoxin - pharmacology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia disorders; Drug Interactions; Elapid Venoms - pharmacology; Female; Hemostatics - pharmacology; Humans; Ionomycin - pharmacology; Ionophores - pharmacology; Male; Medical sciences; Middle Aged; Neurology; Potassium; Potassium Channel Blockers; Potassium Channels - metabolism; Rubidium; Rubidium - metabolism; Thrombin - pharmacology; Human; Pharmacologic test; Nervous system diseases; Calcium; Pathophysiology; Alzheimer disease; Cerebral disorder; Platelet; Central nervous system disease; Degenerative disease; Anomaly; Inhibitor; Potassium
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(98)03200-0

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. 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. 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 α-dendrotoxin (voltage-sensitive K + channels). However, 86Rb + efflux from the platelets of patients with Alzheimer-type dementia was not inhibited by either apamin or charybdotoxin. By contrast, inhibition by α-dendrotoxin did occur. 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.