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

Lancet. 1998 Nov 14;352(9140):1590-3. doi: 10.1016/S0140-6736(98)03200-0.

Abstract

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.

Findings: 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.

Interpretation: 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.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / physiopathology
  • Analysis of Variance
  • Apamin / pharmacology*
  • Case-Control Studies
  • Cells, Cultured
  • Charybdotoxin / pharmacology*
  • Drug Interactions
  • Elapid Venoms / pharmacology*
  • Female
  • Hemostatics / pharmacology
  • Humans
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Male
  • Middle Aged
  • Potassium Channel Blockers*
  • Potassium Channels / metabolism*
  • Rubidium / metabolism*
  • Thrombin / pharmacology

Substances

  • Elapid Venoms
  • Hemostatics
  • Ionophores
  • Potassium Channel Blockers
  • Potassium Channels
  • Charybdotoxin
  • Apamin
  • Ionomycin
  • dendrotoxin
  • Thrombin
  • Rubidium