Influence of a threonine residue in the S2 ligand binding domain in determining agonist potency and deactivation rate of recombinant NR1a/NR2D NMDA receptors

摘要: NR1/NR2D NMDA receptors display unusually slow deactivation kinetics which may be critical for their role as extrasynaptic receptors. A threonine to alanine point mutation has been inserted at amino acid position 692 of the NR2D subunit (T692A). Recombinant NR1a/NR2D(T692A) have expressed in Xenopus laevis oocytes and pharmacological single-channel properties examined using two-electrode voltage-clamp patch-clamp recording techniques. Glutamate dose–response curves from receptor channels produced an approximately 1600-fold reduction glutamate potency compared wild-type NR1a/NR2D There was no change Hill slopes or gross mean maximal currents recorded expressing either mutant The did not affect co-agonist glycine. shifts by NR2D(T692A) containing when activated other glutamate-site agonists such aspartate were 30- 60-fold wild-type. Single-channel conductance levels indistinguishable NR2D-containing channels. Additionally showed transitional asymmetry that is characteristic Rapid applications on outside-out patches macroscopic current deactivations about faster than Our results suggest this conserved residue plays a crucial ligand binding NR2 subunits supports idea decay associated with can explained dissociation subtype.