Identifying the role of GluN2A in cerebral ischemia

Abstract

The activity of the NMDA receptor (NMDAR), which is a glutamate-gated ion channel, is a key factor influencing the neuronal damage following cerebral ischemia. NMDAR is composed of two essential GluN1 subunits and two regionally localized GluN2 or GluN3 subunits. GluN1, GluN2A, and GluN2B are the primary NMDAR subunits in the adult forebrain. Thus, the three major NMDAR subtypes in the adult forebrain are the GluN1/2A receptor, the GluN1/2B receptor, and the GluN1/2A/2B receptor. The functional properties of these NMDARs depend mainly on the GluN2 subunits, and many studies primarily classify NMDARs as GluN2A- and GluN2B-containing NMDARs. However, given the influence of the triheteromeric GluN1/2A/2B receptor, this misclassification might lead to a misunderstanding of the physiological and pathological roles of GluN2, especially the GluN2A subunit. Understanding the role of the GluN1/2A/2B receptor in cerebral ischemia may be critical for identifying the specific role of the GluN2A subunit, which may mediate pro-survival effects following cerebral ischemia.