L-type calcium channels in the hippocampus and cerebellum of Alzheimer's disease brain tissue

There is growing evidence that the selective neuronal cell death observed i n Alzheimer's Disease (AD) is the result of dysregulation of intracellular calcium (Ca2+) homeostasis. In the present study, L-type voltage sensitive calcium channels (L-VSCCs) were examined in the cerebellum and hippocampus of AD (n = 6; postmortem interval less than 5 h) and age-matched control (n = 6) tissue by homogenate binding techniques and quantitative in vitro rec eptor autoradiography using [H-3]isradipine (PN200-110), saturation analyse s of the cerebellum revealed unaltered [H-3]isradipine binding parameters ( K-d and B-max) between AD and control subjects. Analysis of AD and control hippocampus demonstrated significant differences as [H-3]isradipine binding increased (62%) in AD, whereas hippocampal cell density decreased (29%) in AD, relative to control subjects. Moreover, AD differentially affected L-V SCC in area CA1 and dentate gyrus. The dentate gyrus had greatly increased binding (77%) with little cell loss (16%) in AD brains, whereas area CA1 ha d increased binding (40%) with significant cell loss (42%) in AD brains, re lative to controls. The results of the present study suggest that hippocamp al area CAI may experience greater cell loss in response to increased L-VSC Cs in AD relative to other brain regions. (C) 2000 Elsevier Science Inc. Al l rights reserved.