Neurotoxicity of Aβ amyloid protein in vitro is not altered by calcium channel blockade

In cortical cultures, Aβ protein destabilizes calcium homeostasis, but direct neurotoxicity of Aβ is not observed. In hippocampal cultures, we and others find treatment with Aβ protein decreases neuronal survival, but the mechanism of neurotoxicity is unknown. We have used low-density, serum-free cultures of hippocampal neurons to determine whether the neurotoxicity of Aβ protein in vitro can be altered by voltage- or ligand-gated calcium channel antagonists or cyclic nucleotides. In these cultures, neither ω-conotoxin, nifedipine, verapamil, APV, nor MK-801 altered the survival of neurons exposed to synthetic Aβ 1–40. The N-channel antagonist diltiazem decreased Aβ 1–40 toxicity repeatedly, but slightly, perhaps by indirectly contributing to increased neuronal viability. Treatment of cultures with dibutyryl cAMP, 8-bromo cAMP, dibutyryl cGMP, and 8-bromo cGMP also failed to alter Aβ toxicity. Thus, the toxicity of beta protein in low-density hippocampal cultures was not directly altered either by calcium channel blockers or by the addition of cyclic nucleotides.