Glutamate-induced increases in intracellular free Mg2+ in cultured cortical neurons

Intracellular free Mg2+ concentrations ([Mg2+]i) in single rat brain neurons were measured with the Mg(2+)-sensitive fluorescent dye magfura-2. Addition of glutamate with glycine raised [Mg2+]i from 1 to more than 11 mM compared with the resting concentration of 0.5 mM, an effect mediated by N-methyl-D-aspartate receptors. Most of the increase in [Mg2+]i was independent of extracellular Mg2+, but was dependent on extracellular Ca2+. The second component of the increase induced by glutamate was independent of extracellular Ca2+, but required extracellular Mg2+ and was amplified by extracellular Na+ removal. These results indicate that regulation of [Mg2+]i by neurotransmitters such as glutamate may be important in controlling neuronal excitability.