REDUCTION OF CEREBRAL CORTICAL [H-3] OUABAIN BINDING-SITE (NA-ATPASE)DENSITY IN DEMENTIA AS EVALUATED IN FRESH HUMAN CEREBRAL CORTICAL BIOPSIES(,K+)

Na+,K+-ATPase density in human cerebral cortex was for the first time studied by vanadate facilitated [H-3]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 hydr ocephalus (NPH) syndrome and associated dementia. For control measurem ents post-mortem samples were obtained from patients without clinicall y observed dementia. [H-3]ouabain binding kinetics were evaluated: whe n incubating samples in 1 mu M [H-3]ouabain binding equilibrium was ob tained after 6 h of incubation, non-specific uptake and retention amou nted to only 2.3% of total uptake and retention of [H-3]ouabain and re lease of specifically bound [H-3]ouabain during washout in the cold oc curred only slowly (T-1/2 = 37 h). Evaluation of receptor affinity for ouabain was in agreement with a heterogeneous population of [H-3]ouab ain binding sites. [H-3]ouabain binding was significantly reduced afte r frozen storage of samples before measurements. Post-mortem degradati on of cerebral [H-3]ouabain binding sites occurred only slowly (T-1/2 = 75 h). No significant variation in [H-3]ouabain binding site density was observed between the cerebral lobes with occipital, parietal and temporal values (means +/- S.E.M., n = 5) amounting to 10 281 +/- 649, 11 267 +/- 1011 and 9263 +/- 615 pmol/g wet wt., respectively. [H-3]O uabain binding measured in frontal cortical samples gave values of (me ans +/- S.E.M., n = 5) 4274 +/- 1020 and 11 397 +/- 976 pmol/g wet wt. (triangle% = 62; P < 0.05) in patients with dementia and controls, re spectively. Human cerebral cortical capacity for active K+ uptake was around 37- and 16-fold greater than in skeletal muscular and myocardia l tissue, respectively.