Compression and stretch sensitive submucosal neurons of the porcine and human colon

Anna Katharina Filzmayer,Michael Schemann,Klaus Michel,Kristin Elfers,Sabine Buhner,Gemma Mazzuoli-Weber,Florian Zeller,Jörg Theisen,Ihsan Ekin Demir

doi:10.1038/s41598-020-70216-6

Abstract

The pig is commonly believed to be a relevant model for human gut functions—however, there are only a few comparative studies and none on neural control mechanisms. To address this lack we identified as one central aspect mechanosensitive enteric neurons (MEN) in porcine and human colon. We used neuroimaging techniques to record responses to tensile or compressive forces in submucous neurons. Compression and stretch caused Ca-transients and immediate spike discharge in 5–11% of porcine and 15–24% of human enteric neurons. The majority of these MEN exclusively responded to either stimulus quality but about 9% responded to both. Most of the MEN expressed choline acetyltransferase and substance P; nitric oxide synthase-positive MEN primarily occurred in distal colon. The findings reveal common features of MEN in human and pig colon which we interpret as a result of species-independent evolutionary conservation rather than a specific functional proximity between the two species.

Highlights

The pig is commonly believed to be a relevant model for human gut functions—there are only a few comparative studies and none on neural control mechanisms
Supplementary Video 1 shows an example of intraganglionic injection into a porcine submucosal ganglion of the proximal colon containing compression sensitive mechanosensitive enteric neurons (MEN) responding to this stimulus with action potential discharge
We confirmed our hypothesis on the presence of MEN in the submucosal plexus (SMP) of the porcine and human colon

Summary

Introduction

The pig is commonly believed to be a relevant model for human gut functions—there are only a few comparative studies and none on neural control mechanisms To address this lack we identified as one central aspect mechanosensitive enteric neurons (MEN) in porcine and human colon. Compression and stretch caused Ca-transients and immediate spike discharge in 5–11% of porcine and 15–24% of human enteric neurons The majority of these MEN exclusively responded to either stimulus quality but about 9% responded to both. Our hypothesis is that MEN exist in the ISMP of the porcine and human colon This is supported by studies that showed nerve-mediated chloride secretion in laboratory animal models in response to distension of mucosal-submucosal preparations[25,26,27,28]. These are second-order neurons, as the sensory cell transducing the stimulus is the enterochromaffin cell, which activates serotonin (1P) receptors on submucosal primary afferent neurons by releasing serotonin[29]

Methods

Results

Conclusion