Increased expression of NR2A subunit does not alter NMDA-evoked responses in cultured fetal trisomy 16 mouse hippocampal neurons.
The trisomy 16 (Ts16) mouse is an animal model for human trisomy 21 (Down's syndrome). The gene encoding the NR2A subunit of the NMDA receptor has been localized to mouse chromosome 16. In the present study, western blot analysis revealed a 2.5-fold increase of NR2A expression in cultured Ts16 embryonic hippocampal neurons. However, this increase did not affect the properties of NMDA-evoked currents in response to various modulators. The sensitivity of NMDA receptors to transient applications of NMDA, spermine, and Zn(2+) was investigated in murine Ts16 and control diploid cultured embryonic hippocampal neurons. Peak and steady-state currents evoked by NMDA were potentiated by spermine at concentrations < 1 mM, and inhibited by Zn(2+) in a dose-dependent and voltage-independent manner. No marked difference was observed between Ts16 and control diploid neurons for any of these modulators with regard to IC(50) and EC(50) values or voltage dependency. Additionally, inhibition by the NR2B selective inhibitor, ifenprodil, was similar. These results demonstrate that NMDA-evoked currents are not altered in cultured embryonic Ts16 neurons and suggest that Ts16 neurons contain similar functional properties of NMDA receptors as diploid control neurons despite an increased level of NR2A expression.
Klein
R C
RC
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Siarey
R J
RJ
Caruso
A
A
Rapoport
S I
SI
Castellino
F J
FJ
Galdzicki
Z
Z
D000818:Animals; D002874:Chromosome Mapping; D004171:Diploidy; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006579:Heterozygote; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D013096:Spermine / Q000494:pharmacology; D014314:Trisomy; D015032:Zinc / Q000494:pharmacology
C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D016202:N-Methylaspartate; D015032:Zinc