Modification of NMDA receptor channels and synaptic transmission by targeted disruption of the NR2C gene.
A novel strain of mutant mouse has been generated with a deletion of the gene encoding the NR2C subunit of the NMDA receptor, which is primarily expressed in cerebellar granule cells. Patch-clamp recordings from granule cells in thin cerebellar slices were used to assess the consequences of the gene deletion. In granule cells of wild-type animals, a wide range of single-channel conductances were observed (19-60 pS). The disruption of the NR2C gene results in the disappearance of low-conductance NMDA receptor channels ( < 37 pS) normally expressed in granule cells during developmental maturation. The NMDA receptor-mediated synaptic current is markedly potentiated in amplitude, but abbreviated in duration (with no net difference in total charge), and the non-NMDA component of the synaptic current was reduced. We conclude that the NR2C subunit contributes to functional heteromeric NMDA receptor-subunit assemblies at the mossy fiber synapse and extrasynaptic sites during maturation, and the conductance level exhibited by a given receptor macromolecule may reflect the stochiometry of subunit composition.
Ebralidze
A K
AK
Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge 02139-4307, USA.
Rossi
D J
DJ
Tonegawa
S
S
Slater
N T
NT
D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D004553:Electric Conductivity; D018390:Gene Targeting; D005796:Genes; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate