MUTAGENESIS RESCUES SPERMINE AND ZN2+ POTENTIATION OF RECOMBINANT NMDA RECEPTORS

Alternative splicing generates distinct forms of the NMDA receptor sub unit NR1. NR1 subunits with an N-terminal insert (termed N1) form rece ptors in Xenopus oocytes with greatly reduced potentiation by spermine and Zn2+. Oocytes expressing NR1 receptors with N1 exhibited larger N MDA currents than oocytes expressing corresponding receptors without N 1. In the present study, we used mutational analysis to investigate st ructural features of the N1 insert that control current amplitude and spermine and Zn2+ potentiation. Neutralization of positive charges in N1 rescued spermine and Zn2+ potentiation. Positive charges in N1 did not affect spermine or Zn2+ affinity. Neutralization of positive charg es in N1 diminished the responses to the level of NR1 receptors lackin g N1. The positively charged N1 may increase NMDA currents by causing a conformational change similar to that produced by spermine and Zn2in NR1 receptors lacking N1.