Ca2+ channel blockers attenuate beta-amyloid peptide toxicity to cortical neurons in culture.

Deposit of beta-amyloid protein (A beta) in Alzheimer's disease brain may contribute to the associated neurodegeneration. We have studied the neurotoxicity of A beta in primary cultures of murine cortical neurons, with the aim of identifying pharmacologic ways of attenuating the injury. Exposure of cultures to A beta (25-35 fragment; 3-25 microM) generally triggers slow, concentration-dependent neurodegeneration (over 24-72 h). With submaximal A beta-(25-35) exposure (10 microM), substantial (> 40% within 48 h) degeneration often occurs and is markedly attenuated by the presence of the Ca2+ channel blockers nimodipine (1-20 microM) and Co2+ (100 microM) during the A beta exposure. However, A beta neurotoxicity is not affected by the presence of glutamate receptor antagonists. We suggest that Ca2+ influx through voltage-gated Ca2+ channels may contribute to A beta-induced neuronal injury and that nimodipine and Co2+, by attenuating such influx, are able to attenuate A beta neurotoxicity.