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The Journal of Neurophysiology Vol. 87 No. 4 April 2002, pp. 2052-2063
Copyright ©2002 by the American Physiological Society
1Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037; 2Department of Neurobiology and 3Program in Neuroscience,Harvard Medical School, Boston 02115; 4CNS Research Institute, Brigham and Women's Hospital, Boston, Massachusetts 02115; 5Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62702; and 6Department of Biology and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Hong Kong, Special Administrative Region, China
Sasaki, Yasnory F.,
Thomas Rothe,
Louis S. Premkumar,
Saumya Das,
Jiankun Cui,
Maria V. Talantova,
Hon-Kit Wong,
Xiandi Gong,
Shing Fai Chan,
Dongxian Zhang,
Nobuki Nakanishi,
Nikolaus J. Sucher, and
Stuart A. Lipton.
Characterization and Comparison of the NR3A Subunit of
the NMDA Receptor in Recombinant Systems and Primary Cortical Neurons. J. Neurophysiol. 87: 2052-2063, 2002. Recently, we cloned and began to characterize a new
N-methyl-D-aspartate receptor (NMDAR) subunit,
NR3A. Here we extend our earlier findings by showing that recombinantly
expressed NR3A in COS cells is biochemically associated with both NR1
and NR2 subunits. In the oocyte or HEK 293 cell expression systems,
co-injection of NR3A with NR1/NR2 subunits acts in a
dominant-interfering manner, resulting in a decrease in NMDAR unitary
conductance, decrease in Ca2+ permeability,
decrease in Mg2+ sensitivity, and slight increase
in mean open time compared with NR1/NR2 channels. The smaller unitary
conductance channel has also been observed in primary cortical neurons
cultured from wild-type rodent on postnatal day 8 (P8) and similarly found to be relatively insensitive to
Mg2+ block. Consistent with these findings, whole
cell NMDA-evoked currents are larger in NR3A-deficient mice compared
with wild-type mice, and this effect follows a developmental pattern
similar to that of NR3A protein expression on Western blots, with peak expression at P8. Finally, a new longer splice variant of
NR3A has been cloned and found to be expressed in rodent cortical
neurons by single-cell RT-PCR and in situ hybridization.
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