Coupling of permeation and gating in an NMDA-channel pore mutant.
We report a strong coupling between permeation and gating in a mutant NMDA channel (NR1 N598Q-NR2A). The channel opens to two states that differ by their conductance and, surprisingly, by their selectivity for two permeant monovalent cations, Na+ and Cs+. The two open states are linked to the closed state via a cyclic gating reaction that proceeds preferentially in one direction under biionic conditions, indicating that the gating mechanism is not at equilibrium. The direction and the magnitude of this gating asymmetry can be accounted for by assuming that ions bound to a site in the permeation pathway influence the gating of this mutant channel, and that in the closed state, the channel site is accessible to internal cations.
Schneggenburger
R
R
Ecole Normale Supérieure, Laboratoire de Neurobiologie, Paris, France.
Ascher
P
P
D000818:Animals; D002586:Cesium / Q000378:metabolism; D003001:Cloning, Molecular; D004553:Electric Conductivity; D005260:Female; D005998:Glycine / Q000494:pharmacology; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D016202:N-Methylaspartate / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014982:Xenopus laevis
D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D002586:Cesium; D016202:N-Methylaspartate; D012964:Sodium; D005998:Glycine