NMDA Receptor-Mediated Ca²⁺ Flux Attenuated by the NMDA Receptor/TRPM4 Interface Inhibitor Brophenexin.

ABSTRACT: Transient receptor potential melastatin-4 (TRPM4) forms a complex with N-methyl-D-aspartate receptors (NMDARs) that facilitates NMDAR-mediated neurotoxicity. Here we used pharmacological tools to determine how TRPM4 regulates NMDAR signaling. Brophenexin, a compound that binds to TRPM4 at the NMDAR binding interface, protected hippocampal neurons in culture from NMDA-induced death, consistent with published work. Brophenexin (10 μM) reduced NMDA-evoked whole-cell currents recorded at 22°C by 87% ± 14% with intracellular Ca²⁺ chelated to prevent TRPM4 activation. Brophenexin inhibited NMDA-evoked currents recorded in Na⁺-free solution by 87% ± 13%, suggesting that brophenexin and TRPM4 modulate NMDAR function. Incubating cultures in Mg²⁺-free buffer containi

SUBMITTER: Casby J 

PROVIDER: S-EPMC11582383 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature