多个AMPA受体电导状态的配体依赖性开放：协同模型
Ligand-dependent opening of the multiple AMPA receptor conductance states: a concerted model
摘要：
突触后膜AMPA受体的调节是脊椎动物中枢神经系统中突触可塑性背后的主要机制之一。单通道激动剂刺激的电生理记录表明，重组和天然AMPA受体访问多个电导状态的激动剂浓度依赖性的方式。我们提出了一个基于四个亚基协同构象转变的多电导状态的变构模型，就像虹膜一样。我们的模型预测，热力学行为的电导状态后，完全和部分激动剂刺激可以描述与受体的亲和力增加，因为它们进展到更高的电导状态。该模型还预测了AMPA受体在非配体导电substates的存在。然而，自发开口的概率随着电导的增加而降低。最后，我们预测，大电导状态是稳定的上升期内的全细胞EPSC的海马神经元中。我们的模型提供了一个机制的配体浓度和电导状态之间的联系，可以解释AMPA受体门控的热力学和动力学特征。
英文摘要：
Modulation of the properties of AMPA receptors at the post-synaptic membrane is one of the main suggested mechanisms behind synaptic plasticity in the central nervous system of vertebrates. Electrophysiological recordings of single channels stimulated with agonists showed that both recombinant and native AMPA receptors visit multiple conductance states in an agonist concentration dependent manner. We propose an allosteric model of the multiple conductance states based on concerted conformational transitions of the four subunits, as an iris diaphragm. Our model predicts that the thermodynamic behaviour of the conductance states upon full and partial agonist stimulations can be described with increased affinity of receptors as they progress to higher conductance states. The model also predicts existence of AMPA receptors in non-liganded conductive substates. However, spontaneous openings probability decreases with increasing conductances. Finally, we predict that the large conductance states are stabilized within the rise phase of a whole-cell EPSC in glutamatergic hippocampal neurons. Our model provides a mechanistic link between ligand concentration and conductance states that can explain thermodynamic and kinetic features of AMPA receptor gating.
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