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A Newly Identified Population of Gastrointestinal Neurons Expressing HCN4 Regulates Retrograde Peristalsis

38 Pages Posted: 21 May 2019 Sneak Peek Status: Review Complete

See all articles by Kensuke Fujii

Kensuke Fujii

Osaka Medical College - Department of General and Gastroenterological Surgery

Koichi Nakajo

Osaka Medical College - Department of Physiology; Jichi Medical University - Division of Integrative Physiology, Department of Physiology

Yoshihiro Egashira

Osaka Medical College - Department of Physiology

Yasuhiro Yamamoto

Osaka Medical College - Department of Physiology

Kohei Taniguchi

Osaka Medical College - Department of General and Gastroenterological Surgery

Masaru Kawai

Osaka Medical College - Department of General and Gastroenterological Surgery

Hideki Tomiyama

Osaka Medical College - Department of General and Gastroenterological Surgery

Koichi Kawakami

National Institute of Genetics - Laboratory of Molecular and Developmental Biology; Graduate University for Advanced Studies (SOKENDAI) - Department of Genetics

Kazuhisa Uchiyama

Osaka Medical College - Department of General and Gastroenterological Surgery

Fumihito Ono

Osaka Medical College - Department of Physiology

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Abstract

Peristalsis is indispensable for physiological function of the gut. Enteric nervous system (ENS) plays an important role in regulating the peristalsis. While the neural network regulating the anterograde peristalsis, which migrates from the oral end to the anal end, is characterized to some extent, the retrograde peristalsis remains unresolved with regards to its neural regulation. Using forward genetics in zebrafish, we revealed that a population of neurons expressing a hyperpolarization-activated nucleotide-gated channel HCN4 specifically regulates retrograde peristalsis. HCN4(+) neurons are serotonergic, and are observed along the entire length of the gut. When blocked by a HCN channel inhibitor, retrograde peristalsis was specifically attenuated. Conversely, when HCN4(+) neurons expressing channelrhodopsin were activated by illumination, retrograde peristalsis was enhanced while anterograde peristalsis remained unchanged. Moreover, the effect of blocker or illumination was limited to the circular muscle, as opposed to the longitudinal muscle, resulting in the specific change of movement transverse to the gut axis. We propose that HCN4(+) neurons in the ENS forward activating signals toward the oral end and simultaneously stimulate local circuits regulating the circular muscle.

Keywords: HCN4, 5HT, Enteric nervous system, Retrograde peristalsis, Zebrafish, Optogenetics, Channelrhodopsin

Suggested Citation

Fujii, Kensuke and Nakajo, Koichi and Egashira, Yoshihiro and Yamamoto, Yasuhiro and Taniguchi, Kohei and Kawai, Masaru and Tomiyama, Hideki and Kawakami, Koichi and Uchiyama, Kazuhisa and Ono, Fumihito, A Newly Identified Population of Gastrointestinal Neurons Expressing HCN4 Regulates Retrograde Peristalsis (May 20, 2019). CELL-REPORTS-D-19-01580. Available at SSRN: https://ssrn.com/abstract=3391468 or http://dx.doi.org/10.2139/ssrn.3391468
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kensuke Fujii

Osaka Medical College - Department of General and Gastroenterological Surgery ( email )

Japan

Koichi Nakajo

Osaka Medical College - Department of Physiology ( email )

Japan

Jichi Medical University - Division of Integrative Physiology, Department of Physiology ( email )

Japan

Yoshihiro Egashira

Osaka Medical College - Department of Physiology

Japan

Yasuhiro Yamamoto

Osaka Medical College - Department of Physiology

Japan

Kohei Taniguchi

Osaka Medical College - Department of General and Gastroenterological Surgery

Japan

Masaru Kawai

Osaka Medical College - Department of General and Gastroenterological Surgery

Japan

Hideki Tomiyama

Osaka Medical College - Department of General and Gastroenterological Surgery

Japan

Koichi Kawakami

National Institute of Genetics - Laboratory of Molecular and Developmental Biology

Japan

Graduate University for Advanced Studies (SOKENDAI) - Department of Genetics

Japan

Kazuhisa Uchiyama

Osaka Medical College - Department of General and Gastroenterological Surgery

Japan

Fumihito Ono (Contact Author)

Osaka Medical College - Department of Physiology ( email )

Japan

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