NR2 subunit-depenclence of NMDA receptor channel block by external Mg2+
NR2 subunit-depenclence of NMDA receptor channel block by external Mg2+
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DOI：
10.1113/jphysiol.2004.076737
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发表时间：
2005-01-15
影响因子：
5.5
通讯作者：
Johnson, JW
中科院分区：
文献类型：
--
作者：
Qian, A;Buller, AL;Johnson, JW
NMDA受体在中枢神经系统生理中的重要作用主要依赖于外部Mg~（2+）（Mg-o（2+））对电压依赖性通道的阻断。Mg-o（2+）对NMDA受体通道的阻断依赖于受体亚基的组成：NR1/2A受体（由NR1和NR2A亚基组成的受体）和NR1/2B受体比NR1/2C或NR1/2D受体更强地被Mg-o（2+）抑制。我们研究了Mg-o（2+）对HEK293和293T细胞中表达的重组NR1/2D和NR1/2A受体记录的单通道0和全细胞电流的影响。主要结论如下：（1）在所有电压下，Mg-o（2+）对全细胞NR1/2D受体反应的电压依赖性抑制至少比对NR1/2A受体反应的抑制弱4倍。(2)Mg-o（2+）的通道阻滞减少了NR1/2D受体单通道开放的持续时间;该减少用于估计Mg-o（2+）的表观阻滞率（k（+，app））。NR1/2D受体的k（+，app）与在所有测试电压下从由NR1、NR2A和NR2B亚基组成的皮层NMDA受体获得的k+，app相似，但略慢。(3)Mg-o（2+）阻断事件在闭合持续时间分布中诱导了额外的分量;该分量用于估计Mg-o（2+）的表观解除阻断率（k（-，app））。在所有测试电压下，NR1/2D受体的k（-，app）比皮质受体的k（-，app）快得多。NR1/2D和皮层受体的k（-，app）的电压依赖性不同，表明Mg-o（2+）可能比皮层受体更容易渗透NR1/2D受体。(4)Mg-o（2+）对NR1/2D受体的抑制作用不如皮层受体，这主要是因为Mg-o（2+）与NR1/2D受体的解结合要快得多。
The vital roles played by NMDA receptors in CNS physiology depend critically on powerful voltage-dependent channel block by external Mg2+ (Mg-o(2+)). NMDA receptor channel block by Mg-o(2+) depends on receptor subunit composition: NR1/2A receptors (receptors composed of NR1 and NR2A subunits) and NR1/2B receptors are more strongly inhibited by Mg-o(2+) than are NR1/2C or NR1/2D receptors. We investigated the effects of Mg-o(2+) on single-channel 0 and whole-cell currents recorded from recombinant NR1/2D and NR1/2A receptors expressed in HEK293 and 293T cells. The main conclusions are as follows: (1) Voltage-dependent inhibition by Mg-o(2+) of whole-cell NR1/2D receptor responses was at least 4-fold weaker than inhibition of NR1/2A receptor responses at all voltages tested. (2) Channel block by Mg-o(2+) reduced the duration of NR1/2D receptor single-channel openings; this reduction was used to estimate the apparent blocking rate of Mg-o(2+)(k(+,app)). The k(+,app) for NR1/2D receptors was similar to but moderately slower than the k+,app obtained from cortical NMDA receptors composed of NR1, NR2A and NR2B subunits at all voltages tested. (3) Mg-o(2+) blocking events induced an additional component in the closed-duration distribution; this component was used to estimate the apparent unblocking rate of Mg-o(2+) (k(-,app)). The k(-,app) for NR1/2D receptors was much faster than the k(-,app) for cortical receptors at all voltages tested. The voltage-dependence of the k(-,app) of NR1/2D and cortical receptors differed in a manner that suggested that Mg-o(2+) may permeate NR1/2D receptors more easily than cortical receptors. (4) Mg-o(2+) inhibits NR1/2D receptors less effectively than cortical receptors chiefly because Mg-o(2+) unbinds much more rapidly from NR1/2D receptors.