The kinetic properties of the α3 rat glycine receptor make it suitable for mediating fast synaptic inhibition
The kinetic properties of the α3 rat glycine receptor make it suitable for mediating fast synaptic inhibition
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DOI：
10.1113/jphysiol.2013.252189
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发表时间：
2013-07-01
影响因子：
5.5
通讯作者：
Sivilotti, Lucia G.
中科院分区：
文献类型：
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作者：
Marabelli, Alessandro;Moroni, Mirko;Sivilotti, Lucia G.
甘氨酸受体介导脊髓和脑干中的快速突触抑制。两个α亚单位存在于成年神经元中，α 1，其形成大多数突触甘氨酸受体，和α 3。α 3的生理作用尚不清楚，尽管事实上α 3表达集中在涉及伤害性处理的区域，如浅表背角。在本研究中，我们的特点是在HEK293细胞中异源表达的大鼠同型α 3甘氨酸受体的动力学特性。我们通过拟合动力学方案分析了在一系列不同甘氨酸浓度下的稳态单通道活性，发现α 3通道类似于α 1受体，具有高的最大开放概率（99.1% cf. 98%），但不同之处在于当所有五个结合位点都被甘氨酸占据时达到最大开放概率（cf.α 1的五个位点中的三个）。α 3激活最好用动力学方案描述，该方案允许通道在部分配体化时也打开，并且包含多于最小数目的关闭状态，作为脱敏的远端状态（Jones和Westbrook方案）或作为预打开门控中间体（翻转方案）。我们还记录了突触样α 3电流引起的快速应用1毫秒脉冲的高浓度甘氨酸外向补丁。这些电流具有快速失活，衰减的时间常数为9 ms。因此，如果原生突触电流可以由α 3甘氨酸受体介导，则它们可能在其动力学中非常接近α 1介导的突触事件。
Glycine receptors mediate fast synaptic inhibition in spinal cord and brainstem. Two alpha subunits are present in adult neurones, alpha 1, which forms most of the synaptic glycine receptors, and alpha 3. The physiological role of alpha 3 is not known, despite the fact that alpha 3 expression is concentrated in areas involved in nociceptive processing, such as the superficial dorsal horn. In the present study, we characterized the kinetic properties of rat homomeric alpha 3 glycine receptors heterologously expressed in HEK293 cells. We analysed steady state single channel activity at a range of different glycine concentrations by fitting kinetic schemes and found that alpha 3 channels resemble alpha 1 receptors in their high maximum open probability (99.1% cf. 98% for alpha 1), but differ in that maximum open probability is reached when all five binding sites are occupied by glycine (cf. three out of five sites for alpha 1). alpha 3 activation was best described by kinetic schemes that allow the channel to open also when partially liganded and that contain more than the minimum number of shut states, either as desensitized distal states (Jones and Westbrook scheme) or as pre-open gating intermediates (flip scheme). We recorded also synaptic-like alpha 3 currents elicited by the rapid application of 1 ms pulses of high concentration glycine to outside-out patches. These currents had fast deactivation, with a time constant of decay of 9 ms. Thus, if native synaptic currents can be mediated by alpha 3 glycine receptors, they are likely to be very close in their kinetics to alpha 1-mediated synaptic events.