The NR3B subunit does not alter the anesthetic sensitivities of recombinant N-methyl-D-aspartate receptors
The NR3B subunit does not alter the anesthetic sensitivities of recombinant N-methyl-D-aspartate receptors
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DOI：
10.1213/01.ane.0000152324.30272.49
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发表时间：
2005-06-01
影响因子：
5.7
通讯作者：
Sakimura, K
中科院分区：
文献类型：
--
作者：
Yamakura, T;Askalany, AR;Sakimura, K
N-甲基-D-天冬氨酸（NMDA）受体NR 3B亚基与NR 1和NR 2亚基共组装形成具有不同通道特性的受体复合物。在本研究中，我们研究了NR 3B亚基共表达对爪蟾卵母细胞中表达的NR 1/NR 2通道的NMDA受体麻醉敏感性的影响。虽然NR 3B亚基显著降低了NR 1/NR 2A-B通道的电流幅度，但NR 1/NR 2A-B通道对Mg 2+、氯胺酮、异氟烷、一氧化二氮和乙醇的敏感性并不因NR 3B亚基的共表达而改变。这些结果表明，NMDA受体的麻醉敏感性不依赖于NR 3亚基的存在或不存在。NR 3B亚基中与NR 1和NR 2亚基中的N和N + 1位点同源的两个氨基酸残基的突变（其构成Mg 2+和氯胺酮的阻断位点）不影响NR 1/NR 2B/NR 3B通道对Mg 2+、氯胺酮和异氟烷的敏感性。因此，NR 3亚基中N和N + 1位点的氨基酸残基不太可能参与NR 1/NR 2/NR 3通道中通道阻断位点的形成。
The N-methyl-D-aspartate (NMDA) receptor NR3B subunit co-assembles with NR1 and NR2 subunits to form a receptor complex with distinct channel properties. In the present study, we investigated the effects of co-expression of the NR3B subunit on the anesthetic sensitivities of NMDA receptors for NR1/NR2 channels expressed in Xenopus oocytes. Although the NR3B subunit prominently reduced the current amplitude of NR1/NR2A-B channels, the sensitivities of NR1/ NR2A-B channels to Mg2+, ketamine, isoflurane, nitrous oxide, and ethanol were not altered by coexpression of the NR3B subunit. These results suggest that the anesthetic sensitivities of NMDA receptors do not depend on the presence or absence of the NR3 subunit. Mutations of two amino acid residues in the NR3B subunit at positions homologous to the N and N + 1 sites in the NR1 and NR2 subunits, which constitute the blocking sites for Mg2+ and ketamine, did not affect the sensitivities of NR1/NR2B/NR3B channels to Mg2+, ketamine and isoflurane. Thus, the amino acid residues at the N and N + 1 sites in NR3 subunits are unlikely to be involved in the formation of channel blocking sites in NR1/NR2/NR3 channels.