Intestinal distension orchestrates neuronal activity in the enteric nervous system of adult mice.

Autor: Cavin JB; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.; Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada.; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada., Wongkrasant P; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.; Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada.; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada., Glover JB; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.; Live Cell Imaging Laboratory, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Balemba OB; Department of Biological Sciences, University of Idaho, Moscow, ID, USA., MacNaughton WK; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.; Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada.; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada., Sharkey KA; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2023 Apr; Vol. 601 (7), pp. 1183-1206. Date of Electronic Publication: 2023 Feb 20.
DOI: 10.1113/JP284171
Abstrakt: The enteric nervous system (ENS) regulates the motor, secretory and defensive functions of the gastrointestinal tract. Enteric neurons integrate mechanical and chemical inputs from the gut lumen to generate complex motor outputs. How intact enteric neural circuits respond to changes in the gut lumen is not well understood. We recorded intracellular calcium in live-cell confocal recordings in neurons from intact segments of mouse intestine in order to investigate neuronal response to luminal mechanical and chemical stimuli. Wnt1-, ChAT- and Calb1-GCaMP6 mice were used to record neurons from the jejunum and colon. We measured neuronal calcium response to KCl (75 mM), veratridine (10 μM), 1,1-dimethyl-4-phenylpiperazinium (DMPP; 100 μM) or luminal nutrients (Ensure®), in the presence or absence of intraluminal distension. In the jejunum and colon, distension generated by the presence of luminal content (chyme and faecal pellets, respectively) renders the underlying enteric circuit unresponsive to depolarizing stimuli. In the distal colon, high levels of distension inhibit neuronal response to KCl, while intermediate levels of distension reorganize Ca 2+ response in circumferentially propagating slow waves. Mechanosensitive channel inhibition suppresses distension-induced Ca 2+ elevations, and calcium-activated potassium channel inhibition restores neuronal response to KCl, but not DMPP in the distended colon. In the jejunum, distension prevents a previously unknown tetrodotoxin-resistant neuronal response to luminal nutrient stimulation. Our results demonstrate that intestinal distension regulates the excitability of ENS circuits via mechanosensitive channels. Physiological levels of distension locally silence or synchronize neurons, dynamically regulating the excitability of enteric neural circuits based on the content of the intestinal lumen. KEY POINTS: How the enteric nervous system of the gastrointestinal tract responds to luminal distension remains to be fully elucidated. Here it is shown that intestinal distension modifies intracellular calcium levels in the underlying enteric neuronal network, locally and reversibly silencing neurons in the distended regions. In the distal colon, luminal distension is integrated by specific mechanosensitive channels and coordinates the dynamics of neuronal activation within the enteric network. In the jejunum, distension suppresses the neuronal calcium responses induced by luminal nutrients. Physiological levels of distension dynamically regulate the excitability of enteric neuronal circuits.
(© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)
Databáze: MEDLINE
Externí odkaz: