Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis
Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis
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DOI：
10.1016/j.celrep.2020.02.024
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发表时间：
2020-03-03
期刊：
影响因子：
8.8
通讯作者：
Ono, Fumihito
中科院分区：
文献类型：
--
作者：
Fujii, Kensuke;Nakajo, Koichi;Ono, Fumihito
蠕动对于肠道的生理功能是不可或缺的。肠神经系统(ENS)在肠蠕动调节中起着重要作用。虽然从口端到肛端的神经网络对顺行蠕动的调节有一定的特点，但关于逆行蠕动的神经调节仍未得到解决。利用斑马鱼的正向遗传学，我们揭示了一群表达超极化激活的核苷酸门控通道HCN4的神经元特异性地调节逆行蠕动。当HCN4通道被HCN通道抑制剂或吗啉阻断蛋白表达时，逆行蠕动被特异性地减弱。相反，当表达通道视紫红质的HCN4(+)神经元被光照激活时，逆行蠕动增强，而顺行蠕动保持不变。我们认为，ENS中的HCN4(+)神经元向口腔末端转发激活信号，同时刺激调节环行肌的局部回路。
Peristalsis is indispensable for physiological function of the gut. The enteric nervous system (ENS) plays an important role in regulating peristalsis. While the neural network regulating anterograde peristalsis, which migrates from the oral end to the anal end, is characterized to some extent, retrograde peristalsis remains unresolved with regards to its neural regulation. Using forward genetics in zebrafish, we reveal that a population of neurons expressing a hyperpolarization-activated nucleotide-gated channel HCN4 specifically regulates retrograde peristalsis. When HCN4 channels are blocked by an HCN channel inhibitor or morpholinos blocking the protein expression, retrograde peristalsis is specifically attenuated. Conversely, when HCN4(+) neurons expressing channelrhodopsin are activated by illumination, retrograde peristalsis is enhanced while anterograde peristalsis remains unchanged. We propose that HCN4(+) neurons in the ENS forward activating signals toward the oral end and simultaneously stimulate local circuits regulating the circular muscle.