Protons inhibit Cd potentiation of NMDA receptors with M3 helix Cys substitutions. (A and B) Whole-cell currents evoked at pH 8.0 (A) or pH 6.6 (B) by 10 µM NMDA and glycine (open bars) alone or together with 400 µM Cd (cyan bars) in HEK293 cells cotransfected with N1 L10C and either N2B WT (A) or N2A WT (B). (C) Summary plot of currents (mean ± SEM, four to seven cells per construct) evoked at −80 and +60 mV by NMDA + glycine + Cd as a fraction of NMDA + glycine alone, at pH 8.0 or pH 6.6. The difference between pH 8.0 and pH 6.6 was significant for each construct combination (paired t test). In addition, at pH 8.0, the (I N+g+Cd / I N+g) ratio was significantly larger for N1A8C coexpressed with N2A WT than with N2B WT (t test).