Reduction of cerebral cortical [3H]ouabain binding site (Na+,K(+)-ATPase) density in dementia as evaluated in fresh human cerebral cortical biopsies.
Na+,K(+)-ATPase density in human cerebral cortex was for the first time studied by vanadate facilitated [3H]ouabain binding to intact samples. Fresh human cerebral cortical biopsies were obtained as a result of diagnostic frontal lobe biopsy from patients with normal pressure hydrocephalus (NPH) syndrome and associated dementia. For control measurements post-mortem samples were obtained from patients without clinically observed dementia. [3H]ouabain binding kinetics were evaluated: when incubating samples in 1 microM [3H]ouabain binding equilibrium was obtained after 6 h of incubation, non-specific uptake and retention amounted to only 2.3% of total uptake and retention of [3H]ouabain and release of specifically bound [3H]ouabain during washout in the cold occurred only slowly (T1/2 = 37 h). Evaluation of receptor affinity for ouabain was in agreement with a heterogeneous population of [3H]ouabain binding sites. [3H]Ouabain binding was significantly reduced after frozen storage of samples before measurements. Post-mortem degradation of cerebral [3H]ouabain binding sites occurred only slowly (T1/2 = 75 h). No significant variation in [3H]ouabain binding site density was observed between the cerebral lobes with occipital, parietal and temporal values (means +/- S.E.M., n = 5) amounting to 10281 +/- 649, 11267 +/- 1011 and 9263 +/- 615 pmol/g wet wt., respectively. [3H]Ouabain binding measured in frontal cortical samples gave values of (means +/- S.E.M., n = 5) 4274 +/- 1020 and 11397 +/- 976 pmol/g wet wt. delta % = 62; P < 0.05) in patients with dementia and controls, respectively. Human cerebral cortical capacity for active K+ uptake was around 37- and 16-fold greater than in skeletal muscular and myocardial tissue, respectively.
Schmidt
T A
TA
Department of Medicine B 2142, Rigshospitalet, National University Hospital, Copenhagen, Denmark.
Hasselbalch
S
S
Larsen
J S
JS
Bundgaard
H
H
Juhler
M
M
Kjeldsen
K
K
D000368:Aged; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003704:Dementia / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010042:Ouabain / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase