Agonist-specific gating of NMDA receptors

Gating reaction mechanism of neuronal NMDA receptors.

The activation mechanisms of recombinant N-methyl-d-aspartate receptors (NRs) have been established in sufficient detail to account for their single channel and macroscopic responses; however, the reaction mechanism of native NRs remains uncertain due to indetermination of the isoforms expressed and possible neuron-specific factors. To delineate the activation mechanism of native NRs, we examin...

Tweaking agonist efficacy at NMDA receptors by site-directed mutagenesis

NMDA receptor subunit gating--uncovered.

Kinetically distinct contributions of NMDA receptor NR1 and NR2 subunits to channel gating have recently been inferred by Banke and Traynelis from single-channel recordings of recombinant NR1–NR2B receptors. The results suggest a new mechanism for receptor activation that will enhance our insight into excitatory synaptic transmission in the brain. In the post-genomic era, this represents an exc...

Target-Specific Expression of Presynaptic NMDA Receptors in Neocortical Microcircuits

Traditionally, NMDA receptors are located postsynaptically; yet, putatively presynaptic NMDA receptors (preNMDARs) have been reported. Although implicated in controlling synaptic plasticity, their function is not well understood and their expression patterns are debated. We demonstrate that, in layer 5 of developing mouse visual cortex, preNMDARs specifically control synaptic transmission at py...

Cell type-specific pharmacology of NMDA receptors using masked MK801

N-Methyl-D-aspartate receptors (NMDA-Rs) are ion channels that are important for synaptic plasticity, which is involved in learning and drug addiction. We show enzymatic targeting of an NMDA-R antagonist, MK801, to a molecularly defined neuronal population with the cell-type-selectivity of genetic methods and the temporal control of pharmacology. We find that NMDA-Rs on dopamine neurons are nec...