Binding sites, singly bound states, and conformation coupling shape GABA-evoked currents
Binding sites, singly bound states, and conformation coupling shape GABA-evoked currents
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DOI：
10.1152/jn.00951.2002
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发表时间：
2003-02-01
影响因子：
2.5
通讯作者：
Zarnowska, ED
中科院分区：
文献类型：
--
作者：
Mozrzymas, JW;Barberis, A;Zarnowska, ED
GABA诱发电流的时程是GABA（A）受体门控的主要信息来源。由于这些电流的动力学取决于几个受体构象之间的转换，它是一个重大的挑战，以确定电流动力学和微观门控方案的各自的速率常数之间的关系。本研究的目的是进一步探索不同的GABA（A）受体构象对超快GABA应用引起的电流动力学的影响。我们表明GABA诱发电流的上升相位和幅度取决于脱敏和单束缚态。结合受体的占有率不仅取决于结合特性，还取决于打开/关闭和脱敏。通道状态之间的这种功能性耦合的影响在突触传递的典型高度非平衡条件下是关键的。GABA引起的电流的上升相的浓度依赖性表明激动剂结合位点之间的正协同性。我们提供的证据表明，在低GABA浓度的预平衡减少GABA诱发的电流，由于受体捕获在一个单一的绑定脱敏状态。
The time course of GABA-evoked currents is the main source of information on the GABA(A) receptor gating. Since the kinetics of these currents depends on the transitions between several receptor conformations, it is a major challenge to define the relations between current kinetics and the respective rate constants of the microscopic gating scheme. The aim of this study was to further explore the impact of different GABA(A) receptor conformations on the kinetics of currents elicited by ultra-fast GABA applications. We show that the rising phase and amplitude of GABA-evoked currents depend on desensitization and singly bound states. The occupancy of bound receptors depends not only on binding properties but also on opening/closing and desensitization. The impact of such functional coupling between channel states is critical in conditions of high non-equilibrium typical for synaptic transmission. The concentration dependence of the rising phase of the GABA-elicited current indicates positive cooperativity between agonist binding sites. We provide evidence that preequilibration at low GABA concentrations reduce GABA-evoked currents due to receptor trapping in a singly bound desensitized state.