Amyloid beta-peptide (A beta P) potentiates a nimodipine-sensitive L-type barium conductance in N1E-115 neuroblastoma cells.

The neurodegenerative pathology observed in Alzheimer's Disease (AD) has been partially attributed to the neurotoxic effects of the amyloid beta-peptide (A beta P), although the mechanisms underlying this neurotoxicity are unknown. Since A beta P is capable of forming cation channels in lipid bilayers, it is possible that the neurotoxic effects on neurons may be mediated by a cation flux. We have used patch-clamp recording techniques to study the effects of A beta P on cation currents in differentiated mouse N1E-115 neuroblastoma cells.

X-ray diffraction analysis of brain lipid membrane structure in Alzheimer's disease and beta-amyloid peptide interactions.

Small angle x-ray diffraction analysis of Alzheimer's disease (AD) lipid membranes reconstituted from cortical gray matter showed significant, reproducible structure changes relative to age-matched control samples. Specifically, there was an average 4 A reduction in the lipid bilayer width and marked changes in membrane electron density profiles of AD cortical samples. There were no significant structure differences in the membrane bilayers isolated from an unaffected region (cerebellum) of the AD brain.

Evidence for changes in the Alzheimer's disease brain cortical membrane structure mediated by cholesterol.

Small angle X-ray diffraction analysis of Alzheimer's disease (AD) lipid membranes extracted from cortical gray matter showed significant, reproducible structure changes relative to age-matched control samples. Specifically, there was an average 4 A reduction in the lipid bilayer width and significant changes in the membrane electron density profiles of AD cortical samples. There were no significant structure differences in the membrane bilayers isolated from an unaffected region (cerebellum) of the AD brain.

Cholesterol alters the binding of Ca2+ channel blockers to the membrane lipid bilayer.

X-ray diffraction and equilibrium binding techniques were used to study the effect of cholesterol on membrane binding of the charged 1,4-dihydropyridine (DHP) Ca2+ channel antagonist amlodipine and uncharged isradipine, nimodipine, and nitrendipine. Increases in membrane cholesterol content resulted in a marked decrease in DHP binding to cardiac phospholipid membranes, as expressed by the equilibrium partition coefficient (Kp[mem]). Between a 0:1 and 0.