Amyloid-β promotes calcium influx and neurodegeneration via stimulation of L voltage-sensitive calcium channels rather than NMDA channels in cultured neurons
Affiliations: [a] Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts, Lowell, Lowell, MA 01854, USA | [b] Department of Biochemistry, University of Massachusetts, Lowell, Lowell, MA 01854, USA | [c] Department of Biological Sciences, University of Massachusetts, Lowell, Lowell, MA 01854, USA
Abstract: Exposure of cultured neurons and neuronal cells to aggregated amyloid-β (Aβ) induces multiple neurodegenerative events including accumulation of cytosolic calcium, generation of reactive oxygen species, abnormal levels of phosphorylation of the microtubule-associated protein tau, and apoptosis. Prevention of accumulation of calcium within the cytosol also prevents all other events, suggesting that calcium accumulation is an early and pivotal event in Aβ neurotoxicity. Calcium influx has been suggested to occur via L voltage-sensitive calcium channels or NMDA channels. Calcium influx into differentiated human neuroblastoma cells has been previously attributed to the L voltage-sensitive calcium channel, but the contribution of the NMDA channel was not examined. In the present study, treatment of these cells with MK-801, an antagonist of NMDA channels, failed to attenuate Aβ-induced calcium influx or neurodegeneration, while nimopridine, an antagonist of the L voltage-sensitive calcium channel, blocked Aβ-induced calcium influx. Our findings suggest that NMDA channels do not contribute significantly to Aβ neurotoxicity in these acute cell culture analyses.
