Intestinal Ca2+ wave dynamics in freely moving C elegans coordinate execution of a rhythmic motor program
Intestinal Ca2+ wave dynamics in freely moving C elegans coordinate execution of a rhythmic motor program
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DOI：
10.1152/ajpcell.00303.2007
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发表时间：
2008-01-01
影响因子：
5.5
通讯作者：
Mowrey, William
中科院分区：
文献类型：
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作者：
Nehrke, K.;Denton, Jerod;Mowrey, William
在线虫秀丽隐杆线虫中，排便是一种高度节律性的行为，由肠上皮细胞中产生的Ca 2+波调节，部分通过激活肌醇1，4，5-三磷酸受体。排便运动程序（排便运动程序）的执行可以通过外部提示（如营养可用性或机械刺激）进行修改。为了解决的可能性，环境调节的肠道需要整合不同的细胞和有机体的过程中，我们已经开发出一种方法来研究协调钙振荡和排便行为在完整的，自由行为的动物。我们通过检查已知改变Ca 2+处理的基因中的突变[包括egl-8/磷脂酶C（PLC）-β、kqt-3/KCNQ 1、sca-1/肌浆网Ca 2 + ATP酶和unc-43/Ca 2 +-CaMKII]如何有助于形成Ca 2+波来测试这种技术，并询问突变背景中的Ca 2+波动力学如何改变了神经元的执行。值得注意的是，我们发现在没有PLC β的情况下，Ca 2+波异位启动，通常反向传播，并且未能触发完全的电刺激。这些结果表明，正常的优势后肠细胞是不是强制性的钙波的发生，而是有助于协调钙。此外，我们提出的证据表明，潜在的起搏器似乎以比排便周期更快的频率振荡，心律失常可能是由于起搏器与排便周期解偶联，而不是破坏起搏器本身。我们还表明，慢性升高的Ca 2+排便期的影响有限，而是改变连续步骤之间的间隔的排便。最后，我们的研究结果表明，它是可能的，以评估Ca 2+动力学和肌肉收缩在一个完全不受限制的模型生物。
Defecation in the nematode worm Caenorhabditis elegans is a highly rhythmic behavior that is regulated by a Ca2+ wave generated in the 20 epithelial cells of the intestine, in part through activation of the inositol 1,4,5-trisphosphate receptor. Execution of the defecation motor program (DMP) can be modified by external cues such as nutrient availability or mechanical stimulation. To address the likelihood that environmental regulation of the DMP requires integrating distinct cellular and organismal processes, we have developed a method for studying coordinate Ca2+ oscillations and defecation behavior in intact, freely behaving animals. We tested this technique by examining how mutations in genes known to alter Ca2+ handling [including egl-8/phospholipase C (PLC)-beta, kqt-3/KCNQ1, sca-1/sarco (endo) plasmic reticulum Ca2+ ATPase, and unc-43/Ca2+-CaMKII] contribute to shaping the Ca2+ wave and asked how Ca2+ wave dynamics in the mutant backgrounds altered execution of the DMP. Notably, we find that Ca2+ waves in the absence of PLC beta initiate ectopically, often traveling in reverse, and fail to trigger a complete DMP. These results suggest that the normal supremacy of the posterior intestinal cells is not obligatory for Ca2+ wave occurrence but instead helps to coordinate the DMP. Furthermore, we present evidence suggesting that an underlying pacemaker appears to oscillate at a faster frequency than the defecation cycle and that arrhythmia may result from uncoupling the pacemaker from the DMP rather than from disrupting the pacemaker itself. We also show that chronic elevations in Ca2+ have limited influence on the defecation period but instead alter the interval between successive steps of the DMP. Finally, our results demonstrate that it is possible to assess Ca2+ dynamics and muscular contractions in a completely unrestrained model organism.