NMDA receptor NR2 subunit dependence of the slow component of magnesium unblock
NMDA receptor NR2 subunit dependence of the slow component of magnesium unblock
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DOI：
10.1523/jneurosci.0577-06.2006
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发表时间：
2006-05-24
影响因子：
5.3
通讯作者：
Johnson, Jon W.
中科院分区：
文献类型：
--
作者：
Clarke, Richard J.;Johnson, Jon W.
NMDA受体活性对于许多生理功能是重要的，包括突触形成和突触强度的改变。NMDA受体通常由NR 1和NR 2亚基组成。有四个NR 2亚基（NR 2A-NR 2D）。NR 2亚基的表达在大脑区域和发育阶段各不相同。功能性NMDA受体内NR 2亚基的身份有助于确定许多药理学和生物物理学受体特性，包括外部Mg 2+（Mgo（2+））的阻断强度。Mgo（2+）阻断对NMDA受体介导的反应具有强烈的电压依赖性，并且对于NMDA受体在中枢神经系统内发挥的许多功能至关重要。在这里，我们描述了NR 2亚基依赖的快速去极化后的Mgo（2+）解除阻断的动力学。我们发现，Mgo（2+）从NR 1/2A和NR 1/2B受体中释放出一个显著的慢成分，类似于先前在天然海马和皮层NMDA受体中描述的。引人注目的是，这种缓慢的Mgo（2+）解除阻断的组分在NR 1/2C和NR 1/2D受体中完全不存在。因此，来自NR 1/2C和NR 1/2D受体的电流比来自NR 1/2A和NR 1/2B受体的电流对快速去极化的响应更快。此外，Mgo（2+）从NR 1/2B受体解除阻断的慢组分始终比从NR 1/2A受体解除阻断的慢。这使得快速去极化，如动作电位波形，更有效地刺激Mgo（2+）从NR 1/2A比从NR 1/2B受体解除阻滞。这些NR 2亚基在Mgo（2+）解除阻断动力学中的差异可能有助于确定每个NMDA受体亚型在突触活动期间对电流流动的贡献。
NMDA receptor activity is important for many physiological functions, including synapse formation and alterations in synaptic strength. NMDA receptors are composed most commonly of NR1 and NR2 subunits. There are four NR2 subunits (NR2A - NR2D). NR2 subunit expression varies across both brain regions and developmental stages. The identity of the NR2 subunit within a functional NMDA receptor helps to determine many pharmacological and biophysical receptor properties, including strength of block by external Mg2+ (Mgo(2+)). Mgo(2+) block confers strong voltage dependence to NMDA receptor-mediated responses and is critically important for many of the functions that the NMDA receptor plays within the CNS. Here we describe the NR2 subunit dependence of the kinetics of Mgo(2+) unblock after rapid depolarizations. We find that Mgo(2+) unblocks from NR1/2A and NR1/2B receptors with a prominent slow component similar to that previously described in native hippocampal and cortical NMDA receptors. Strikingly, this slow component of Mgo(2+) unblock is completely absent from NR1/2C and NR1/2D receptors. Thus currents from NR1/2C and NR1/2D receptors respond more rapidly to fast depolarizations than currents from NR1/2A and NR1/2B receptors. In addition, the slow component of Mgo(2+) unblock from NR12B receptors is consistently slower than from NR1/2A receptors. This makes rapid depolarizations, such as action potential waveforms, more efficacious at stimulating Mgo(2+) unblock from NR1/2A than from NR1/2B receptors. These NR2 subunit differences in the kinetics of Mgo(2+) unblock are likely to help determine the contribution of each NMDA receptor subtype to current flow during synaptic activity.