Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity
Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity
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DOI：
10.1038/ncomms2626
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发表时间：
2013-03-01
影响因子：
16.6
通讯作者：
Saur, Dieter
中科院分区：
文献类型：
--
作者：
Klein, Sabine;Seidler, Barbara;Saur, Dieter
肠道神经系统包括兴奋性和抑制性神经元，它们控制着平滑肌细胞的收缩和松弛以及胃肠运动活动。神经信号转导到肠道平滑肌细胞的确切细胞机制还知之甚少。在这里，我们产生了一个c-Kit(CreERT2)敲入等位基因，以靶向一组不同的起搏细胞，称为Cajal间质细胞。通过遗传功能丧失的研究，我们发现，Cajal间质细胞产生自发的电慢波，从而导致平滑肌的节律性收缩，对于将信号从肠神经传递到胃肠道平滑肌细胞是必不可少的。因此，Cajal间质细胞将兴奋性和抑制性神经传递与慢波活动结合起来，协调肠道的蠕动活动。Cajal间质细胞功能受损会导致严重的胃肠运动障碍。我们的研究结果表明，在遗传水平上，这些疾病不仅是由于慢波活动的丧失，而且是由于神经传递的障碍。
The enteric nervous system contains excitatory and inhibitory neurons, which control contraction and relaxation of smooth muscle cells as well as gastrointestinal motor activity. Little is known about the exact cellular mechanisms of neuronal signal transduction to smooth muscle cells in the gut. Here we generate a c-Kit(CreERT2) knock-in allele to target a distinct population of pacemaker cells called interstitial cells of Cajal. By genetic loss-of-function studies, we show that interstitial cells of Cajal, which generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature, are essential for transmission of signals from enteric neurons to gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore, integrate excitatory and inhibitory neurotransmission with slow-wave activity to orchestrate peristaltic motor activity of the gut. Impairment of the function of interstitial cells of Cajal causes severe gastrointestinal motor disorders. The results of our study show at the genetic level that these disorders are not only due to loss of slow-wave activity but also due to disturbed neurotransmission.