Density-dependent changes of the pore properties of the P2X2 receptor channel
Density-dependent changes of the pore properties of the P2X2 receptor channel
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DOI：
10.1113/jphysiol.2004.064568
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发表时间：
2004-07-01
影响因子：
5.5
通讯作者：
Kubo, Y
中科院分区：
文献类型：
--
作者：
Fujiwara, Y;Kubo, Y
配体门控离子通道是突触传递的基础并在突触传递中发挥重要作用，并且通常认为离子通道孔具有能够严格调节离子渗透的刚性结构。一个例外是P2X ATP门控通道。在应用ATP后，P2X（2）通道的离子选择性随时间发生变化，即对大阳离子的渗透性逐渐增加，并且内向整流的强度存在显著的细胞间差异。在这里，我们发现P2X（2）通道特性与表达水平相关：卵母细胞中P2X（2）表达水平的增加增加了对大阳离子的渗透性，减少了内向整流并增加了配体敏感性。我们还观察到，内向整流的变化呈剂量依赖性的方式，即当低浓度的ATP施加到一个高表达水平的卵母细胞，内向整流的诱发电流的强度是弱的。综上所述，这些结果表明，P2X（2）通道的孔隙性质不是静态的，而是动态变化的依赖于开放通道密度。此外，我们通过突变研究发现，位于孔外口的Ile 328对于P2 X的密度依赖性变化至关重要（2）。我们的研究结果表明，突触传递可以通过局部密度依赖性的通道特性的变化，例如，由集群分子的存在下调制。
Ligand-gated ion channels underlie and play important roles in synaptic transmission, and it is generally accepted that the ion channel pores have a rigid structure that enables strict regulation of ion permeation. One exception is the P2X ATP-gated channel. After application of ATP, the ion selectivity of the P2X(2) channel time-dependently changes, i.e. permeability to large cations gradually increases, and there is significant cell-to-cell variation in the intensity of inward rectification. Here we show P2X(2) channel properties are correlated with the expression level: increasing P2X(2) expression level in oocytes increases permeability to large cations, decreases inward rectification and increases ligand sensitivity. We also observed that the inward rectification changed in a dose-dependent manner, i.e. when low concentration of ATP was applied to an oocyte with a high expression level, the intensity of inward rectification of the evoked current was weak. Taken together, these results show that the pore properties of P2X(2) channel are not static but change dynamically depending on the open channel density. Furthermore, we identified by mutagenesis study that Ile328 located at the outer mouth of the pore is critical for the density-dependent changes of P2X(2). Our findings suggest synaptic transmission can be modulated by the local density-dependent changes of channel properties caused, for example, by the presence of clustering molecules.