NEUROTOXICITY OF A-BETA AMYLOID PROTEIN IN-VITRO IS NOT ALTERED BY CALCIUM-CHANNEL BLOCKADE

In cortical cultures, A beta protein destabilizes calcium homeostasis, but direct neurotoxicity of A beta is not observed. In hippocampal cu ltures, we and others find treatment with A beta protein decreases neu ronal survival, but the mechanism of neurotoxicity is unknown. We have used low-density, serum-free cultures of hippocampal neurons to deter mine whether the neurotoxicity of A beta protein in vitro can be alter ed by voltage- or ligand-gated calcium channel antagonists or cyclic n ucleotides. In these cultures, neither omega-conotoxin, nifedipine, ve rapamil, APV, nor MK-801 altered the survival of neurons exposed to sy nthetic A beta 1-40. The N-channel antagonist diltiazem decreased A be ta 1-40 toxicity repeatedly, but slightly, perhaps by indirectly contr ibuting to increased neuronal viability. Treatment of cultures with di butyryl cAMP, 8-bromo cAMP, dibutyryl cGMP, and 8-bromo cGMP also fail ed to alter A beta toxicity. Thus, the toxicity of beta protein in low -density hippocampal cultures was not directly altered either by calci um channel blockers or by the addition of cyclic nucleotides.