Effects of Mg2+ on recovery of NMDA receptors from inhibition by memantine and ketamine reveal properties of a second site.

ABSTRACT: Memantine and ketamine are NMDA receptor (NMDAR) open channel blockers that are thought to act via similar mechanisms at NMDARs, but exhibit divergent clinical effects. Both drugs act by entering open NMDARs and binding at a site deep within the ion channel (the deep site) at which the endogenous NMDAR channel blocker Mg2+ also binds. Under physiological conditions, Mg2+ increases the IC50s of memantine and ketamine through competition for binding at the deep site. Memantine also can inhibit NMDARs after associating with a second site accessible in the absence of agonist, a process termed second site inhibition (SSI) that is not observed with ketamine. Here we investigated the effects of 1 mM Mg2+ on recovery from inhibition by memantine and ketamine, and on memantine SSI, of the four main

SUBMITTER: Glasgow NG 

PROVIDER: S-EPMC6050087 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature