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DOI：
10.1152/jn.00986.2007
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发表时间：
2008-06
影响因子：
2.5
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中科院分区：
文献类型：
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系统生物学中的一个基本问题是如何将灵活性构建到调节网络中，使它们能够产生依赖于环境的反应。在这里，我们研究了调节节律性运动输出的周期频率（cf）的血清素（5-HT）反应系统的灵活性。我们发现，根据制备方法的不同，同样5分钟的5-HT对加利福尼亚刺龙虾（Panulirus interruptus）幽门网络的浸浴可以产生相对于基线的稳态cf显著增加、减少或无变化。有趣的是，在5-HT应用之前的制备中，平均电路输出没有显着差异。我们开发了药理学工具来检查5-羟色胺反应系统组成部分的制剂对制剂的变异性。我们发现5-HT反应系统至少由三个可分离的成分组成：一个5-HT（2betaPan）样成分介导cf的快速下降，随后持续增加；5-HT（1alphaPan）样成分产生少量且通常逐渐增加的cf；至少有一种与未知受体相关的其他成分介导了cf的持续下降。每种成分产生的cf变化的幅度是高度可变的，因此，当它们相加时，根据制备，它们可能产生cf的净增加、减少或无变化。总的来说，我们的研究表明，5-HT反应系统中相反成分的平衡决定了5-HT诱导的稳态cf相对于基线变化的方向和幅度。
A fundamental question in systems biology addresses the issue of how flexibility is built into modulatory networks such that they can produce context-dependent responses. Here we examine flexibility in the serotonin (5-HT) response system that modulates the cycle frequency (cf) of a rhythmic motor output. We found that depending on the preparation, the same 5-min bath application of 5-HT to the pyloric network of the California spiny lobster, Panulirus interruptus, could produce a significant increase, decrease, or no change in steady-state cf relative to baseline. Interestingly, the mean circuit output was not significantly different among preparations prior to 5-HT application. We developed pharmacological tools to examine the preparation-to-preparation variability in the components of the 5-HT response system. We found that the 5-HT response system consisted of at least three separable components: a 5-HT(2betaPan)-like component mediated a rapid decrease followed by a sustained increase in cf; a 5-HT(1alphaPan)-like component produced a small and usually gradual increase in cf; at least one other component associated with an unknown receptor mediated a sustained decrease in cf. The magnitude of the change in cf produced by each component was highly variable, so that when summed they could produce either a net increase, decrease, or no change in cf depending on the preparation. Overall, our research demonstrates that the balance of opposing components of the 5-HT response system determines the direction and magnitude of 5-HT-induced change in steady-state cf relative to baseline.