Requirement for Glycine in Activation of NMDA-Receptors Expressed in <i>Xenopus</i> Oocytes

TLDR

NMDA receptors play key roles in brain plasticity and pathology, and glycine has been reported to potentiate their responses in neurons and Xenopus oocytes. In Xenopus oocytes expressing NMDA receptors, glycine is essential for channel activation—without it no current is elicited, while 670 nM glycine produces half‑maximal inward currents, and D‑serine and D‑alanine can substitute, highlighting the therapeutic potential of targeting the glycine site.

Abstract

Receptors for N -methyl-D-aspartate (NMDA) are involved in many plastic and pathological processes in the brain. Glycine has been reported to potentiate NMDA responses in neurons and in Xenopus oocytes injected with rat brain messenger RNA. Glycine is now shown to be absolutely required for activation of NMDA receptors in oocytes. In voltage-clamped oocytes, neither perfusion nor rapid pressure application of NMDA onto messenger RNA-injected oocytes caused a distinct ionic current without added glycine. When glycine was added, however, NMDA evoked large inward currents. The concentration of glycine required to produce a half-maximal response was 670 nanomolar, and the glycine dose-response curve extrapolated to zero in the absence of glycine. Several analogs of glycine could substitute for glycine, among which D-serine and D-alanine were the most effective. The observation that D-amino acids are effective will be important in developing drugs targeted at the glycine site.