Block of a small percentage of current by kynurenate suggests that activation of L-Glu receptors partially contributes to D-Asp whole-cell currents, or that D-Asp may activate sharing similar pharmacology to L-Glu receptors. APV

is used extensively in studies investigating synaptic transmission and plasticity associated with learning in GSK1120212 solubility dmso Aplysia (Glanzman 1994; Lin and Glanzman Inhibitors,research,lifescience,medical 1994; Murphy and Glanzman 1997, 1999; Schacher et al. 1997; Conrad et al. 1999; Antonov et al. 2003; Ezzeddine and Glanzman 2003), yet several studies demonstrated no APV sensitivity of putative NMDA-like R responses in Aplysia (Antzoulatos and Byrne 2004; Malkinson and Spira 2010) and Lymnaea (Moroz et al. 1993); L-Glu currents in BSC cells were unaffected by APV. APV had mixed effects on D-Asp-induced currents in subsets of BSC neurons, blocking 22% of the current in most cells while potentiating D-Asp currents an average of two-fold in a minority of cells. While the slight reduction in current in the presence of APV in 68% of BSC neurons Inhibitors,research,lifescience,medical exposed to D-Asp

supports, the hypothesis that NMDAR-like channels are partial contributors to D-Asp whole-cell currents, the absence of APV block of L-GluRs in the same cells counters it. In contrast, the potentiating effect of APV on D-Asp currents in some cells may have been mediated via allosteric modulation of the receptor (Kenakin 2004), in which binding of an antagonist may enhance Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical receptor activation by changing the rank order of agonist potency. The portion of D-Asp current in BSC cells not affected by NMDAR antagonists, as well as the potentiating effect of APV, CNQX, and NBQX, suggests novel, and potentially heterogeneous, D-Asp receptors contribute to the whole cell D-Asp response. PPDA and TCS46b are subunit-specific NMDAR antagonists with PPDA effective in blocking receptors containing NR2C/D subunits (Feng et al. 2004) and TCS46b preferentially blocking

receptors containing NR1A/NR2B subunits (Gregory et al. 2000). PPDA was previously demonstrated to inhibit D-Asp Inhibitors,research,lifescience,medical currents (Carlson and Fieber 2012) and was the strongest blocker of D-Asp currents observed in this study (~45%), while TCS46b had minor, but significant, blocking effects. Thus, D-AspR subunits in Aplysia may be more similar to mammalian NR2C/D than NR2B subunits. In contrast to our results, Errico et al. (2011) did not observe block of D-Asp receptors that implicated specific NMDAR subunits. The nonadditive effects of kynurenate, below PPDA, and APV block on both L-Glu- and D-Asp-activated currents suggests that these antagonists have some binding sites in common on Aplysia L-GluRs and D-AspRs. PPDA block of the two receptors suggests approximately 46% binding of each agonist is pharmacologically similar. The difference in the kynurenate block of the two receptors, however, suggests that an additional approximately 30% of agonist binding is distinct, similar to the findings of Errico et al. (2011).