We report the presence of binding sites for permeant monovalent cations
at the internal and external entrances to the channel of NMDA receptors. We
measured the effects of changing internal cesium (Cs+) and
external sodium (Na+) concentrations on the channel-blocking
kinetics of the adamantane derivatives IEM-1754 and IEM-1857. Binding of Na
+, or of Cs+ after it permeates the channel, to sites
at the external channel entrance prevents blockers from entering the channel.
Binding of Na+ to a blocked channel prevents blocker unbinding.
Cs+ binding to a site at the internal channel entrance prevents
IEM-1754 from occupying the deeper of its two sites of block. The results
show the critical effects of permeant ions on the kinetics, affinity and voltage-dependence
of channel blockers.
