ZFIN ID: ZDB-PUB-200305-10
Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis
Fujii, K., Nakajo, K., Egashira, Y., Yamamoto, Y., Kitada, K., Taniguchi, K., Kawai, M., Tomiyama, H., Kawakami, K., Uchiyama, K., Ono, F.
Date: 2020
Source: Cell Reports   30: 2879-2888.e3 (Journal)
Registered Authors: Kawakami, Koichi, Ono, Fumihito
Keywords: 5HT, HCN4, channelrhodopsin, enteric nervous system, optogenetics, retrograde peristalsis, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Gastrointestinal Motility/drug effects
  • Gastrointestinal Tract/drug effects
  • Gastrointestinal Tract/innervation*
  • Gastrointestinal Tract/physiology
  • Gene Expression Regulation/drug effects
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/antagonists & inhibitors
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism*
  • Larva/drug effects
  • Larva/physiology
  • Morpholinos/pharmacology
  • Neurons/metabolism*
  • Optogenetics
  • Peristalsis*/drug effects
  • Serotonin/metabolism
  • Zebrafish/genetics
  • Zebrafish/physiology*
PubMed: 32130893 Full text @ Cell Rep.
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.