High affinity hippocampal [3H]-glibenclamide binding sites are preserved in Alzheimer's disease.
ATP-sensitive K+ channels were examined in sections of the hippocampus from patients with Alzheimer's disease and age-matched control subjects by means of quantitative autoradiography. ATP-sensitive K+ channels were labelled with the sulfonylurea, [3H]-glibenclamide, which is a potent blocker of these channels. The density of cells in the subiculum and the activity of choline acetyltransferase were determined in the same hippocampal tissue samples. In the hippocampal formation of control subjects, the density of high affinity [3H]-glibenclamide binding sites ranged from 17.6 +/- 0.9 pmoles/g in the presubiculum to 11.6 +/- 0.6 pmoles/g in the parvo-pyramidal layer of the presubiculum. There was no difference between Alzheimer patients and controls in the level of high affinity [3H]-glibenclamide binding in any hippocampal region although there was a marked loss of subicular cells (reduced by 29% compared to controls) and a reduction in choline acetyltransferase activity (reduced by 60% compared to controls). The results suggest that ATP-sensitive K+ channels are associated with elements in the hippocampus which are preserved in Alzheimer's disease.
Ikeda
M
M
Wellcome Surgical Institute & Hugh Fraser Neuroscience Laboratories, University of Glasgow, Scotland, United Kingdom.
Dewar
D
D
McCulloch
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001345:Autoradiography; D001665:Binding Sites; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000378:metabolism* / Q000493:pharmacokinetics; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D016501:Neurites / Q000648:ultrastructure; D010275:Parasympathetic Nervous System / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D002795:Choline O-Acetyltransferase; D005905:Glyburide