Postsynaptic target regulates functional responses induced by 5-HT3 serotonin receptors on axonal varicosities of NG108-15 hybrid neuroblastoma cells.
Postsynaptic target regulates functional responses induced by 5-HT3 serotonin receptors on axonal varicosities of NG108-15 hybrid neuroblastoma cells.
复制标题
突触后靶标调节 5-HT3 血清素受体对 NG108-15 混合神经母细胞瘤细胞轴突静脉曲张诱导的功能反应。
DOI：
10.1016/s0306-4522(00)00512-1
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发表时间：
2001
期刊：
影响因子：
3.3
通讯作者：
Nichols,RA
中科院分区：
文献类型：
--
作者：
Rondé,P;Nichols,RA
大鼠脑突触前5-HT3受体是配体门控离子通道超家族的成员，其引起神经末梢[Ca~(2+)]i变化的方式与躯体5-HT3受体不同。在这里，我们使用杂交神经母细胞瘤细胞系NG108-15作为表达5-HT3受体的模型神经系统，评估突触后靶点在调节突触前受体诱导反应的性质中的作用。用免疫细胞化学方法发现，5-HT3受体存在于分化的NG108-15细胞的突触前突触样索上，表明这些受体具有固有的定位于潜在突触前部位的能力。在缺乏突触后靶点的情况下，定位于精索静脉曲张的5-HT3受体可引起由电压门控钙通道启动的快速而短暂的[钙]i变化，用钙通道阻滞剂评估，这些特性是体细胞5-HT3受体的典型特征。在含有NG108-15细胞形成功能性胆碱能突触的大鼠肌管的共同培养中，5-HT3受体引起的轴索静脉曲张内[Ca~(2+)]i的变化随着时间的推移(3-10天)转移到脑神经末梢：对电压门控钙通道拮抗剂阻断不敏感的持续性反应。用肌管培养的条件培养液模拟NG108-15细胞与肌管共培养的效果。这些结果表明，靶突触后细胞的调节分子决定了突触前5-HT3受体所引起的功能反应。由于靶标诱导的变化需要几天才能显现，我们假设蛋白表达的变化，可能是基因调控变化的结果，是该神经元细胞系轴突静脉曲张对5-HT3受体激活的反应变化的基础。
Rat brain presynaptic 5-HT3serotonin receptors, members of the ligand-gated ion channel superfamily, induce changes in nerve terminal [Ca2+]iin a manner distinct from that found for somatic 5-HT3receptors. Here, we assessed the role of postsynaptic target in regulating the nature of presynaptic receptor-induced responses, using the hybrid neuroblastoma cell line NG108-15 as a model neuronal system that expresses 5-HT3receptors. Using immunocytochemistry, 5-HT3receptors were found to be present on the presynaptic-like varicosities of differentiated NG108-15 cells, indicating that these receptors possess an inherent ability to localize to potential presynaptic sites. In the absence of postsynaptic target, 5-HT3receptors localized to the varicosities induce rapid but transient changes in [Ca2+]ithat were initiated by voltage-gated Ca2+channels, as assessed using Ca2+channel blockers, these properties being typical of those found for somatic 5-HT3receptors. In co-cultures containing rat myotubes, with which NG108-15 cells form functional cholinergic synapses, the 5-HT3receptor-induced changes in [Ca2+]iin the axonal varicosities shifted over time (three to 10 days) to that found for brain nerve endings: sustained responses that were insensitive to blockade by antagonists of voltage-gated Ca2+channels. The effect of co-culturing myotubes with the NG108-15 cells was mimicked by conditioned media from myotube cultures. These results indicate that regulatory molecules from the target postsynaptic cell dictate the functional responses elicited by presynaptic 5-HT3receptors. Because the target-induced changes required several days before they were evident, we hypothesize that changes in protein expression, perhaps the consequence of altered gene regulation, underlie the changes in the responses to 5-HT3receptor activation in the axonal varicosities of this neuronal cell line.