Developmental changes in NMDA receptor glycine affinity and ifenprodil sensitivity reveal three distinct populations of NMDA receptors in individual rat cortical neurons

作者: James N. C. Kew , J. Grayson Richards , Vincent Mutel , John A. Kemp

DOI: 10.1523/JNEUROSCI.18-06-01935.1998

关键词:

摘要: Previous work with recombinant receptors has shown that the identity of NMDA NR2 subunit influences receptor affinity for both glutamate and glycine. We have investigated developmental change in glycine acutely dissociated parietal cortex neurons rat, together expression during ontogeny NR2A NR2B mRNA protein. Whereas there is little age, a population emerges 14- 28-d-old animals markedly reduced (mKD = ∼800 nm) sensitivity to subunit-selective antagonist ifenprodil. These changes are paralleled by increase NR2A. Thus, mature appears lower might not be saturated under normal physiological conditions. Ifenprodil (10 μm) inhibits virtually all receptor-evoked current very young contain single exhibiting high ∼20 nm). In older neurons, which low affinities glycine, ifenprodil high-affinity significant proportion low-affinity component, thus revealing three pharmacologically distinct populations neurons. Moreover, these observations suggest bind containing subunits as well those only NR2B.

参考文章(52)
Kemp J A, Foster A C, Iversen L L, Leeson P D, Woodruff G N, Tridgett R, Priestley T, 7‐クロルキヌレン酸はN‐メチル‐D‐アスパラギン酸受容体複合体のグリシン調節部位での選択的きっ抗物質である Proc Natl Acad Sci USA. ,vol. 85, pp. 6547- 6550 ,(1988)
T. Ishii, K. Moriyoshi, H. Sugihara, K. Sakurada, H. Kadotani, M. Yokoi, C. Akazawa, R. Shigemoto, N. Mizuno, M. Masu, Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. Journal of Biological Chemistry. ,vol. 268, pp. 2836- 2843 ,(1993) , 10.1016/S0021-9258(18)53849-7
CJ McBain, ML Mayer, None, N-methyl-D-aspartic acid receptor structure and function Physiological Reviews. ,vol. 74, pp. 723- 760 ,(1994) , 10.1152/PHYSREV.1994.74.3.723
K. S. Wilcox, R. M. Fitzsimonds, B. Johnson, M. A. Dichter, Glycine regulation of synaptic NMDA receptors in hippocampal neurons Journal of Neurophysiology. ,vol. 76, pp. 3415- 3424 ,(1996) , 10.1152/JN.1996.76.5.3415
F Zafra, C Aragon, L Olivares, NC Danbolt, C Gimenez, J Storm-Mathisen, Glycine transporters are differentially expressed among CNS cells The Journal of Neuroscience. ,vol. 15, pp. 3952- 3969 ,(1995) , 10.1523/JNEUROSCI.15-05-03952.1995
G L Westbrook, P Legendre, Ifenprodil blocks N-methyl-D-aspartate receptors by a two-component mechanism. Molecular Pharmacology. ,vol. 40, pp. 289- 298 ,(1991)
Stéphane Supplisson, Claude Bergman, Control of NMDA Receptor Activation by a Glycine Transporter Co-Expressed inXenopusOocytes The Journal of Neuroscience. ,vol. 17, pp. 4580- 4590 ,(1997) , 10.1523/JNEUROSCI.17-12-04580.1997