Neto2 modulation of kainate receptors with different subunit compositions.

Neto2 modulation of kainate receptors with different subunit compositions.
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DOI:
10.1523/jneurosci.0024-11.2011
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发表时间:
2011-06-01
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
通讯作者:
Howe JR
Howe JR
中科院分区:
其他
文献类型:
--
作者:
Straub C;Zhang W;Howe JR

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与其他谷氨酸受体相比,对盐酸盐受体的了解较少,突触盐酸盐受体显示出与重组受体不同的特性。特别是,海碱盐受体突触电流的缓慢衰减与异种细胞中表达的受体的快速失活和脱敏形成对比。我们最近发现了Neto2作为盐酸盐受体的一个新的辅助亚基,并表明Neto2调节GluK2受体的门控动力学。然而,盐酸盐受体家族由五个不同的亚基(GluK1-5)组成,它们可以形成具有不同功能特性的同质和异质受体。在这里,我们测试了Neto2调制是否随亚基组成而变化。使用快速应用技术将谷氨酸盐应用于含有GluK1、GluK1/5或GluK2/5盐酸盐受体的外向贴片上。Neto2的共表达不同程度地减缓了脱敏。Neto2也减缓了对1 ms谷氨酸脉冲的反应,特别是对于含有GluK5的受体,表达重组盐酸盐受体的神经元的突触后电流也是如此。此外,Neto2显著提高了一些受体脱敏后的恢复速度。这些结果表明Neto2可以调节大多数盐酸盐受体的功能。
Kainate receptors are less well understood than other glutamate receptors, and synaptic kainate receptors display properties that differ from recombinant receptors. In particular, the slow decay of kainate receptor synaptic currents contrasts with the rapid deactivation and desensitization of receptors expressed in heterologous cells. We recently identified Neto2 as a novel accessory subunit of kainate receptors and showed that Neto2 modulates the gating kinetics of GluK2 receptors. However, the kainate receptor family consists of five different subunits (GluK1-5) that can form homomeric and heteromeric receptors with different functional properties. Here we tested if Neto2 modulation varies with subunit composition. Rapid application techniques were used to apply glutamate to outside-out patches that contained GluK1, GluK1/5, or GluK2/5 kainate receptors. Co-expression of Neto2 slowed desensitization to varying degrees. Responses to 1 ms pulses of glutamate were also slowed by Neto2, especially for receptors containing GluK5, as were postsynaptic currents in neurons expressing recombinant kainate receptors. In addition, Neto2 markedly increased the rate at which some receptors recovered from desensitization. These results suggest that Neto2 modulates the function of most kainate receptors.