Role of interstitial cells of Cajal in the generation and modulation of motor activity induced by cholinergic neurotransmission in the stomach

Zhang, Rui Xue; Wang, X. Y.; Chen, D.; Huizinga, Jan D.

doi:10.1111/j.1365-2982.2011.01753.x

Cited by 40 publications

(41 citation statements)

References 52 publications

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“…There has been a long standing controversy whether ICC have a role in the regulation of excitatory and inhibitory neurotransmission, besides generating slow waves [8][9][10][11][12][13][14][15][16]26 . In small intestinal circular smooth muscle cells, ongoing slow waves with a frequency of B30-35 cycles per min (Fig.…”

Section: Icc Depletion Blocks Excitatory Enteric Neurotransmissionmentioning

confidence: 99%

“…Previous studies provided clear evidence that ICC generate a rhythmic pacemaker current, which manifests itself as slow waves in the membrane potential of smooth muscle cells, resulting in rhythmic bowel contractions 4,7,8 . However, a role of ICC in the transmission of excitatory and inhibitory signals from enteric neurons to smooth muscle cells is highly controversial and remains an outstanding question [8][9][10][11][12][13][14][15][16] . This is mainly because of the general lack of models and systems to study ICC function in adult animals at genetic level 9,11,16 .…”

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confidence: 99%

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Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity

et al. 2013

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The enteric nervous system contains excitatory and inhibitory neurons, which control contraction and relaxation of smooth muscle cells as well as gastrointestinal motor activity. Little is known about the exact cellular mechanisms of neuronal signal transduction to smooth muscle cells in the gut. Here we generate a c-Kit CreERT2 knock-in allele to target a distinct population of pacemaker cells called interstitial cells of Cajal. By genetic loss-of-function studies, we show that interstitial cells of Cajal, which generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature, are essential for transmission of signals from enteric neurons to gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore, integrate excitatory and inhibitory neurotransmission with slow-wave activity to orchestrate peristaltic motor activity of the gut. Impairment of the function of interstitial cells of Cajal causes severe gastrointestinal motor disorders. The results of our study show at the genetic level that these disorders are not only due to loss of slow-wave activity but also due to disturbed neurotransmission.

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Section: Icc Depletion Blocks Excitatory Enteric Neurotransmissionmentioning

confidence: 99%

mentioning

confidence: 99%

Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity

et al. 2013

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“…Other studies have shown the degree of stretch of smooth muscle may influence the contractile forces generated in the antrum of rats [15]. Whether or not fibrosis is a useful surrogate for clinical pyloric dysfunction is unknown as there are no data correlating the presence or degree of fibrosis with meaningful clinical standards or metrics of gastric emptying.…”

Section: Degree Of Fibrosismentioning

confidence: 99%

Understanding the Differences Between Gastroparesis and Gastroparesis-Like Syndrome: Filling a GaPing Hole?

Gotfried

Schey

2017

Dig Dis Sci

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“…Whether neuronal input to ICC is significant is a matter of debate, [1][2][3][4][5][6][7]17,26 however growing evidence suggests that ICC play a role in enteric neurotransmission. It has been shown that intramuscular ICC is closely associated with myenteric motor neurons, forming synapse-like junctions with nerve varicosities.…”

Section: Gastrointestinal Motilitymentioning

confidence: 99%

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

et al. 2017

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ABSTRACT. Anticholinergic drugs are well-known to cause adverse effects, such as constipation, but their effects on baseline contractile activity in the gut driven by slow waves is not well established. In a video-based gastrointestinal motility monitoring (GIMM) system, a mouse's small intestine was placed in Krebs solution and recorded using a high definition camera. Untreated controls were recorded for each specimen, then treated with a therapeutic concentration of the drug, and finally, treated with a supratherapeutic dose of the drug. Next, the video clips showing gastrointestinal motility were processed, giving us the segmentation motions of the intestine, which were then converted via Fast Fourier Transform (FFT) into their respective frequency spectrums. These contraction quantifications were analyzed from the video recordings under standardised conditions to evaluate the effect of drugs. Six experimental trials were included with benztropine and promethazine treatments. Only the supratherapeutic dose of benztropine was shown to significantly decrease the amplitude of contractions; at therapeutic doses of both drugs, neither frequency nor amplitude was significantly affected. We have demonstrated that intestinal slow waves can be analyzed based on the colonic frequency or amplitude at a supratherapeutic dose of the anticholinergic medications. More research is required on the effects of anticholinergic drugs on these slow waves to ascertain the true role of ICC in neurologic control of gastrointestinal motility.

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Role of interstitial cells of Cajal in the generation and modulation of motor activity induced by cholinergic neurotransmission in the stomach

Abstract: Pacemaker ICC play a prominent role in the expression of motor activity induced by cholinergic activity and our data suggest that cholinergic neurotransmission to ICC affects the pacemaker frequency.

Cited by 40 publications

References 52 publications

Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity

Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity

Understanding the Differences Between Gastroparesis and Gastroparesis-Like Syndrome: Filling a GaPing Hole?

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

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