Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.
Neuron. 2012 Jun 7;74(5):845-57. doi: 10.1016/j.neuron.2012.04.020.
The kinetics of ligand gated ion channels are tuned to permit diverse roles in cellular signaling. To follow high-frequency excitatory synaptic input, postsynaptic AMPA-type glutamate receptors must recover rapidly from desensitization. Chimeras between AMPA and the related kainate receptors demonstrate that the ligand binding domains alone control the lifetime of the desensitized state. Mutation of nonconserved amino acids in the lower lobe (domain 2) of the ligand binding domain conferred slow recovery from desensitization on AMPA receptors, and fast recovery on kainate receptors. Single-channel recordings and a correlation between the rate of deactivation and the rate of recovery across panels of mutant receptors revealed that domain 2 also controls ion channel gating. Our results demonstrate that the same mechanism that ensures fast recovery also sharpens the response of AMPA channels to synaptically released glutamate.
配体门控离子通道的动力学被调整为允许在细胞信号中发挥多种作用。为了跟随高频兴奋性突触输入，突触后 AMPA 型谷氨酸受体必须从脱敏状态中快速恢复。AMPA 和相关的海人藻酸受体之间的嵌合体表明，配体结合域单独控制脱敏状态的寿命。在配体结合域的下叶（结构域 2）中突变非保守氨基酸，使 AMPA 受体从脱敏状态中缓慢恢复，而使海人藻酸受体快速恢复。单通道记录和突变受体面板之间失活率和恢复率之间的相关性表明，结构域 2 还控制离子通道门控。我们的结果表明，确保快速恢复的相同机制也使 AMPA 通道对突触释放的谷氨酸的反应更加灵敏。
