CONTROL OF PROTON SENSITIVITY OF THE NMDA RECEPTOR BY RNA SPLICING AND POLYAMINES
CONTROL OF PROTON SENSITIVITY OF THE NMDA RECEPTOR BY RNA SPLICING AND POLYAMINES
复制标题
DOI：
10.1126/science.7754371
复制
发表时间：
1995-05-12
期刊：
影响因子：
56.9
通讯作者：
HEINEMANN, SF
中科院分区：
文献类型：
--
作者：
TRAYNELIS, SF;HARTLEY, M;HEINEMANN, SF
N-甲基-D-天冬氨酸（NMDA）-偏好谷氨酸受体的功能可以通过细胞外pH调节，这是一个在脑缺血或癫痫发作期间可能很重要的过程。质子抑制NMDA受体功能的50%，在pH 7.3通过与NR 1亚基的相互作用，和多胺和NR 1外显子5增强受体功能，通过缓解紧张性质子抑制存在于生理pH值。一个单一的氨基酸（赖氨酸211）被确定为介导的影响外显子5在大鼠大脑。在这个位置的电中性取代恢复pH敏感性，因此，多胺缓解紧张性抑制。这种效果，以及多胺和外显子5编码的表面环之间的结构相似性，表明外显子5可能作为一个拴系的pH敏感的NMDA受体功能的组成性调节剂。
The function of the N-methyl-D-aspartate (NMDA)-preferring glutamate receptor can be regulated by extracellular pH, a process that may be important during ischemia in the brain or during seizures. Protons inhibit NMDA receptor function by 50 percent at pH 7.3 through interactions with the NR1 subunit, and both polyamines and NR1 exon 5 potentiate receptor function through relief of the tonic proton inhibition present at physiological pH. A single amino acid (lysine 211) was identified that mediates the effects of exon 5 in the rat brain. Electroneutral substitutions at this position restored pH sensitivity and, consequently, polyamine relief of tonic inhibition. This effect, together with the structural similarities between polyamines and the surface loop encoded by exon 5, suggest that exon 5 may act as a tethered pH-sensitive constitutive modulator of NMDA receptor function.