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

The Alzheimer drug memantine (1-amino-3,5-dimethyl-adamantane) blocks the pore channel of the NMDA receptor. Since memantine also blocks the 5-HT(3) 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 Ca(2+).

Free intracellular Ca(2+) concentrations in whole cells and in saponin-permeabilized cells were monitored spectrofluorometrically in HEK-293 cells stably expressing TRPC6.

Memantine decreased the basal level of intracellular Ca(2+), increased the content of the intracellular Ca(2+) store, which in turn increased the agonist-induced intracellular Ca(2+) release, and increased the store-operated Ca(2+) entry.

In addition to blocking the NMDA receptor, memantine also decreases the basal level of intracellular Ca(2+) and increases the sensitivity of cells to extracellular stimuli. All these effects may be of benefit in the treatment of Alzheimer's disease.