Memantine potentiates agonist-induced Ca2+ responses in HEK 293 cells

Background/Aims: The Alzheimer drug memantine (1-amino-3,5-dimethyl-adamantane) blocks the pore channel of the NMDA receptor. Since memantine also blocks the 5-HT3 receptor, neuronal nicotinic receptor, and voltage-activated Na+ channels, the purpose of our study was to verify whether memantine could influence other types of channels involved in the regulation of Ca2+. Methods: Free intracellular Ca2+ concentrations in whole cells and in saponin-permeabilized cells were monitored spectrofluorometrically in HEK-293 cells stably expressing TRPC6. Results: Memantine decreased the basal level of intracellular Ca2+, increased the content of the intracellular Ca2+ store, which in turn increased the agonist-induced intracellular Ca2+ release, and increased the store-operated Ca2+ entry. Conclusion: In addition to blocking the NMDA receptor, memantine also decreases the basal level of intracellular Ca2+ and increases the sensitivity of cells to extracellular stimuli. All these effects may be of benefit in the treatment of Alzheimer's disease. Copyright (C) 2008 S. Karger AG, Basel.