Memantine Potentiates Agonist-Induced Ca2+ Responses in HEK 293 Cells

Abstract

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.