Multiple inhibitory G-protein-coupled receptors resist acute desensitization in the presynaptic but not postsynaptic compartments of neurons.
Multiple inhibitory G-protein-coupled receptors resist acute desensitization in the presynaptic but not postsynaptic compartments of neurons.
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DOI：
10.1523/jneurosci.1227-12.2012
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发表时间：
2012-07-25
期刊：
影响因子：
--
通讯作者：
Hentges ST
中科院分区：
文献类型：
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作者：
Pennock RL;Dicken MS;Hentges ST
急性脱敏是Gi/o偶联受体的共同特性。然而，最近的数据表明，不同的μ阿片受体（MORs）位于体树突在神经元或在异源系统中表达，MORs在突触前区室的神经元是耐急性脱敏。目前尚不清楚这种差异脱敏是否是许多Gi/o偶联受体的共有特性，也不清楚位于单个细胞类型中的突触前和突触后的受体是否显示差异脱敏。在这里，全细胞记录是由小鼠脑切片中的阿黑皮素原（POMC）神经元制成的。μ阿片类药物，痛敏肽，GABAB受体激动剂诱导的突触后电流，在几分钟内脱敏，而抑制这些受体介导的突触前递质释放保持在整个激动剂暴露。POMC神经元中通道视紫红质2的表达允许从POMC神经元末梢释放光诱发的递质，这通过记录下游神经元中的突触后电流来检测。光诱发电流在所有测试的激动剂的应用中被抑制。因此，在POMC神经元的突触后区室中表达时脱敏的相同受体在位于突触前区室中时抵抗脱敏。MORs的药理学敲低揭示了受体储备的耗竭并不能解释突触前对脱敏的抵抗。在~25%的GABAB激动剂应用的记录中，突触前GABAB受体脱敏，表明对脱敏的抵抗不是由于末端本身的内在特性。总之，这些结果表明，各种突触前受体可以继续发挥作用后，他们的突触后对应物脱敏，并建议隔室特异性修饰可能赋予抵抗脱敏。
Acute desensitization is a common property of Gi/o-coupled receptors. Recent data, however, suggest that unlike mu opioid receptors (MORs) located somato-dendritically in neurons or expressed in heterologous systems, MORs in the presynaptic compartment of neurons are resistant to acute desensitization. It is not yet clear whether this differential desensitization is a shared property of many Gi/o-coupled receptors nor whether receptors located pre- and postsynaptically in a single cell type display differential desensitization. Here, whole-cell recordings were made from proopiomelanocortin (POMC) neurons in mouse brain slices. Agonists for mu opioid, nociceptin, and GABAB receptors induced postsynaptic currents that desensitized within minutes, whereas inhibition of presynaptic transmitter release mediated by these receptors was maintained throughout agonist exposure. Expression of channelrhodopsin2 in POMC neurons allowed for light-evoked transmitter release from POMC neuron terminals which was detected by recording postsynaptic currents in downstream neurons. Light-evoked currents were inhibited throughout the application of all agonists tested. Thus, the same receptors that desensitize when expressed in the postsynaptic compartment of POMC neurons resist desensitization when located in the presynaptic compartment. Pharmacologic knockdown of MORs revealed that depletion of receptor reserve does not account for presynaptic resistance to desensitization. In ~25% of recordings with GABAB agonist application, presynaptic GABAB receptors desensitized suggesting that resistance to desensitization is not due to an intrinsic property of the terminals themselves. Altogether the results indicate that a variety of presynaptic receptors can continue to function after their postsynaptic counterparts desensitize and suggest that a compartment-specific modification may confer resistance to desensitization.