Figure 2.

A, Representative two-electrode voltage-clamp recording of d-serine-mediated current responses at GluRδ2^Lc expressed in Xenopus oocytes. Applications of saturating concentrations of d-serine (30 mm) and the channel blocker 1-naphthyl acetyl spermine (NASP; 100 μm) are indicated by the bars above the current trace. At the beginning of the recording, the baseline currents are predominantly mediated by the spontaneously active GluRδ2^Lc. The spontaneously active GluRδ2^Lc currents are inhibited upon application of a maximally effective concentration of d-serine. Application of the channel blocker NASP results in complete inhibition (100%) of the spontaneously active GluRδ2^Lc current. B, Representative two-electrode voltage-clamp recording of current responses at GluRδ2^Lc R530K. d-Serine at 30 mm minimally reduced spontaneously active currents at GluRδ2^Lc R530K (5%). C, d-Serine at 30 mm reduced the spontaneously active current by 66 ± 2% at GluRδ2^Lc (N = 7) relative to complete inhibition (100%) by NASP. The d-serine response (i.e., d-serine-induced inhibition) was decreased to 5 ± 2% for R530K (N = 9) and 5 ± 1% for D742A (N = 9) relative to complete inhibition (100%) by NASP. In the structure of the GluRδ2 agonist-binding domain in complex with d-serine, the guanidinium group of R530 interacts with the α-carboxyl group of d-serine, and the carboxylate group of D742 interacts with the α-amino group of d-serine.