Disinhibition during myoelectric complexes in the mouse colon

Spencer, Nick J.; Bywater, Robert A.R.; Taylor, Grahame S.

doi:10.1016/s0165-1838(98)00063-0

Cited by 68 publications

(134 citation statements)

References 23 publications

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“…Interestingly, the rise in resting muscle tone is mimicked by the sodium channel blocker TTX (Fida et al, 1997) and is consistent with an inhibitory action of the autoantibody on neural pathways that maintain an inhibitory smooth muscle tone, thought to be mediated predominantly by nitrergic mechanisms (Spencer et al, 1998). Loss of this tonic inhibition results in a disinhibited musculature.…”

Section: Discussionsupporting

confidence: 55%

An Autoantibody in Narcolepsy Disrupts Colonic Migrating Motor Complexes

Jackson¹,

Reed²,

Smith³

et al. 2008

J. Neurosci.

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Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The ex vivo whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.

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Section: Discussionsupporting

confidence: 55%

An Autoantibody in Narcolepsy Disrupts Colonic Migrating Motor Complexes

Jackson¹,

Reed²,

Smith³

et al. 2008

J. Neurosci.

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“…We have recently shown that L. reuteri ingestion facilitates the excitability of myenteric intrinsic sensory neurons (19), which would augment the tonic inhibitory tone that the enteric nervous system exerts on the intestinal circular muscle (12,38,40,50) (see also discussion in Ref. 19).…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli

Ma¹,

Mao²,

Wang³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kunze W. Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli. Am J Physiol Gastrointest Liver Physiol 296: G868 -G875, 2009. First published January 29, 2009 doi:10.1152/ajpgi.90511.2008.-Lactobacillus species ingestion can decrease autonomic responses and spinal fiber discharge to nociceptive colorectal distension (CRD), even in the absence of inflammation. The present study aimed to determine whether dorsal root ganglion (DRG) somas could be a locus where the antinociceptive probiotic may have an effect. Healthy rats were fed with Lactobacillus reuteri or vehicle control for 9 days whereupon they were anesthetized, and intermittent distal colonic CRD at 80 mmHg distension was either performed for 1 h or not. The animals were immediately euthanized and patch-clamp recordings taken after isolation and overnight culture from those DRG that projected to the distal colon. CRD decreased the threshold for action potential generation and increased the number of spikes discharged during a standard depolarizing test stimulus, and this effect was blocked by prior probiotic ingestion. The increase in excitability was paralleled by an increase in DRG capacitance, which was not altered by Lactobacillus reuteri ingestion. CRD did not increase tissue weight or myeloperoxidase activity. We suggest that the effects of CRD may have been caused by activity-dependent neurotransmission between DRG somas. CRD evoked increases in action potential upstroke speed, which suggests that it may also have led to augmentation of sodium channel conductances. Probiotic ingestion may have interfered with this hypothetical mechanism since it blocked the effect of CRD on the action potential. colorectal distension; dorsal root ganglion; probiotics; sensory neurons PROBIOTICS ARE HEALTH-PROMOTING commensal bacteria that can have therapeutic or preventative roles when ingested. Probiotics are most frequently of the Lactobacillus or Bifidobacterium species, and clinically beneficial effects of probiotics have been described in travelers' diarrhea, irritable bowel syndrome, and inflammatory bowel disease (13,29,35,44,46). In addition, probiotics can modulate postinflammatory gut hypersensitivity and alter neuropeptide content (20,43). Because of their therapeutic potential and their presumed consumer safety, the actions of probiotics on the physiological mechanisms underlying peripheral and centrally directed nociceptive signals are increasingly being investigated.Ingestion of probiotic commensals can decrease colorectal distension (CRD)-evoked pain in healthy animals, that is, in the absence of overt inflammation in the intestine. Experimental modulation of intestinal motility (32) and visceral pain (18,32,43) by Lactobacillus species have been convincingly demonstrated for the murine colon. Lactobacillus reuteri (L. reuteri) ingestion can alter the excitability of myenteric intrinsic sensory neurons that were recorded from colon segments taken from healthy rats. Remarkably, in anesthetized he...

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“…Propagating motor complexes occur spontaneously in the isolated colon and can also be triggered by local stimulation (distension or mucosal stroking) (8,22,27,31,35,38,39). These complexes are generated by synchronized firing of populations of ascending and descending myenteric interneurons (40) that activate excitatory motor neurons in a coordinated fashion (37).…”

Section: Myogenic Activity and Carbacholmentioning

confidence: 99%

Neurogenic and myogenic motor activity in the colon of the guinea pig, mouse, rabbit, and rat

Costa

Dodds

Wiklendt

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

106

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Costa M, Dodds KN, Wiklendt L, Spencer NJ, Brookes SJ, Dinning PG. Neurogenic and myogenic motor activity in the colon of the guinea pig, mouse, rabbit, and rat. Am J Physiol Gastrointest Liver Physiol 305: G749 -G759, 2013. First published September 19, 2013 doi:10.1152/ajpgi.00227.2013.-Gastrointestinal motility involves interactions between myogenic and neurogenic processes intrinsic to the gut wall. We have compared the presence of propagating myogenic contractions of the isolated colon in four experimental animals (guinea pig, mouse, rabbit, and rat), following blockade of enteric neural activity. Isolated colonic preparations were distended with fluid, with the anal end either closed or open. Spatiotemporal maps of changes in diameter were constructed from video recordings. Distension-induced peristaltic contractions were abolished by tetrodotoxin (TTX; 0.6 M) in all animal species. Subsequent addition of carbachol (0.1-1 M) did not evoke myogenic motor patterns in the mouse or guinea pig, although some activity was observed in rabbit and rat colon. These myogenic contractions propagated both orally and anally and differed from neurogenic propagating contractions in their frequency, extent of propagation, and polarity. Niflumic acid (300 M), used to block myogenic activity, also blocked neural peristalsis and thus cannot be used to discriminate between these mechanisms. In all species, except the mouse colon, small myogenic "ripple" contractions were revealed in TTX, but in both rat and rabbit an additional, higher-frequency ripple-type contraction was superimposed. Following blockade of enteric nerve function, a muscarinic agonist can evoke propulsive myogenic peristaltic contractions in isolated rabbit and rat colon, but not in guinea pig or mouse colon. Marked differences between species exist in the ability of myogenic mechanisms to propel luminal content, but in all species there is normally a complex interplay between neurogenic and myogenic processes. colon motility; enteric neurons; spatiotemporal maps; peristalsis COLONIC MOTILITY IS CONTROLLED by complex interactive processes in the gut, involving both nerve cells (neurogenic) and spontaneous muscle activity (myogenic). A number of studies have characterized fundamental mechanisms in the colon of the guinea pig, mouse, and rabbit and have shown that propagating contractions underlying peristalsis, or other propulsive motor patterns, require activity in the enteric nervous system (8,11,13,14,17,25).In recent papers, Huizinga et al. (20) and Chen et al. (7) produced evidence that challenges this principle. In the rat colon, in vitro, they showed that, after blocking peristalsis with antagonists of enteric neuronal activity [tetrodotoxin (TTX) or lidocaine], addition of a cholinergic agonist induced a recovery in propagating contractions. From these data they suggested that networks of interstitial cells of Cajal (ICC) work cooperatively with the enteric nervous system to create colonic motor patterns and that the main propulsive mechanism is the ...

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Disinhibition during myoelectric complexes in the mouse colon

Cited by 68 publications

References 23 publications

An Autoantibody in Narcolepsy Disrupts Colonic Migrating Motor Complexes

An Autoantibody in Narcolepsy Disrupts Colonic Migrating Motor Complexes

Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli

Neurogenic and myogenic motor activity in the colon of the guinea pig, mouse, rabbit, and rat

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