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A slow NMDA channel: in search of a role

Stefano Vicini* and Gavin Rumbaugh¹

Recombinant NMDA receptors comprising NR1/NR2D subunits have unique properties when compared with other subtypes. These include low channel conductance with a characteristic pattern of transition between subconductance states and reduced sensitivity to Mg²⁺ blockade. Native NMDA receptors matching the low conductance and Mg²⁺ sensitivity of NR1/NR2D recombinant channels have been found in a few neuronal populations, in particular in developing Purkinje neurons (Momiyama et al. 1996). Ultra-rapid agonist application by means of a piezoelectric translator to excised outside-out membrane patches allows concentration jumps in the milliseconds range similar to those occurring during vesicular synaptic release. The high affinity of glutamate for NR1/NR2D receptors produces an extremely slow channel deactivation in response to brief glutamate applications (Monyer et al. 1994). This property has now been identified for the first time by Misra et al. (this issue of The Journal of Physiology, Misra et al. 2000b) for native NMDA channels in mammalian neurons.