A glutamate concentration-biased allosteric modulator potentiates NMDA-induced ion influx in neurons.

ABSTRACT: Precisely controlled synaptic glutamate concentration is essential for the normal function of the N-methyl D-aspartate (NMDA) receptors. Atypical fluctuations in synaptic glutamate homeostasis lead to aberrant NMDA receptor activity that results in the pathogenesis of neurological and psychiatric disorders. Therefore, glutamate concentration-dependent NMDA receptor modulators would be clinically useful agents with fewer on-target adverse effects. In the present study, we have characterized a novel compound (CNS4) that potentiates NMDA receptor currents based on glutamate concentration. This compound alters glutamate potency and exhibits no voltage-dependent effect. Patch-clamp electrophysiology recordings confirmed agonist concentration-dependent changes in maximum inducible currents. Dyna

SUBMITTER: Costa BM 

PROVIDER: S-EPMC8413904 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature