Cell‐specific effects of nitric oxide on the efficiency and frequency of long distance contractions in murine colon

Abstract

Background Nitric oxide (NO) mediates inhibitory neurotransmission and is a critical component of neuronal programs that generate propulsive contractions. NO acts via its receptor NO‐sensitive guanylyl cyclase (NO‐GC) which is expressed in smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Organ bath studies with colonic rings from NO‐GC knockout mice (GCKO) have indicated NO‐GC to modulate spontaneous contractions. The cell‐specific effects of NO‐GC on the dominant pan‐colonic propulsive contraction, the long distance contractions (LDCs), of whole colon preparations have not yet been described. Methods Contractions of whole colon preparations from wild type (WT), global, and cell‐specific GCKO were recorded. After transformation into spatiotemporal maps, motility patterns were analyzed. Simultaneous perfusion of the colon enabled the correlation of outflow with LDCs to analyze contraction efficiency. Key Results Deletion of NO‐GC in both ICC and SMC (ie, in GCKO and SMC/ICC‐GCKO) caused loss of typical LDC activity and instead generated high‐frequency LDC‐like contractions with inefficient propulsive activity. Frequency was also increased in WT, SMC‐GCKO, and ICC‐GCKO colon in the presence of L‐NAME to block neuronal NO synthase. LDC efficiency was dependent on NO‐GC in SMC as it was reduced in GCKO, SMC‐GCKO, and ICC/SMC‐GCKO colon; LDC efficiency was decreased in all genotypes in the presence of L‐NAME. Conclusions and Inferences NO/cGMP signaling is critical for normal peristaltic movements; as NO‐GC in both SMC and ICC is essential, both cell types appear to work in synchrony. The efficiency of contractions to expel fluid is particularly influenced by NO‐GC in SMC.

Gastrointestinal dysfunction in autism displayed by altered motility and achalasia in Foxp1 +/− mice

“…Whole-Colon Preparation, Isometric Force Studies, Total Gut Transit, and Esophageal Manometry. Colonic motility patterns were recorded and esophageal manometry was performed as described earlier (54,55). A detailed description of the methods is provided in SI Appendix, Materials and Methods.…”

Relationships Between Distention-, Butyrate- and Pellet-Induced Stimulation of Peristalsis in the Mouse Colon

“…The oral and anal ends were cannulated with an 18G needle and then fixed to the platform attached to the floor of the organ bath (Figure 1). The setup was also similar to a previously published photo (Parsons and Huizinga, 2015) and schematic drawing (Beck et al, 2019), for further reference. The oral end was connected to two plastic tubes, and the anal end was attached to a 1 ml syringe without the plunger.…”

“…Colonic motility is dependent on stimuli, and colonic distention is a major stimulus for the initiation of motor patterns. Recently, high-resolution spatio-temporal mapping has given us more insight into motor patterns in the mouse colon (Roberts et al, 2007(Roberts et al, , 2008Vincent et al, 2018;Beck et al, 2019) the rabbit colon (Dinning et al, 2014;Chen et al, 2016) and the human colon (Dinning, 2016;Chen et al, 2017Chen et al, , 2018Corsetti et al, 2017). Despite the fact that luminal stimulation is critical for normal colonic motility, the role of luminal factors in controling or modifying motility has not been extensively studied.…”

Nitric Oxide Is Essential for Generating the Minute Rhythm Contraction Pattern in the Small Intestine, Likely via ICC-DMP

“…(2) Innervation of ICC. Smooth muscle cells receive information via nitrergic innervation of ICC, with the ICC being gap junction coupled to smooth muscle cells (Ward et al, 2004;Lies et al, 2014;Beck et al, 2019). (3) Activity of nitrergic nerves on other nerves within the intestinal neural networks (Furness, 2012;Beck et al, 2018Beck et al, , 2019.…”