Interstitial cells of Cajal and human colon motility in health and disease

Abstract

Our understanding of human colonic motility, and autonomic reflexes that generate motor patterns, has increased markedly through high-resolution manometry. Details of the motor patterns are emerging related to frequency and propagation characteristics that allow linkage to interstitial cells of Cajal (ICC) networks. In studies on colonic motor dysfunction requiring surgery, ICC are almost always abnormal or significantly reduced. However, there are still gaps in our knowledge about the role of ICC in the control of colonic motility and there is little understanding of a mechanistic link between ICC abnormalities and colonic motor dysfunction. This review will outline the various ICC networks in the human colon and their proven and likely associations with the enteric and extrinsic autonomic nervous systems. Based on our extensive knowledge of the role of ICC in the control of gastrointestinal motility of animal models and the human stomach and small intestine, we propose how ICC networks are underlying the motor patterns of the human colon. The role of ICC will be reviewed in the autonomic neural reflexes that evoke essential motor patterns for transit and defecation. Mechanisms underlying ICC injury, maintenance, and repair will be discussed. Hypotheses are formulated as to how ICC dysfunction can lead to motor abnormalities in slow transit constipation, chronic idiopathic pseudo-obstruction, Hirschsprung's disease, fecal incontinence, diverticular disease, and inflammatory conditions. Recent studies on ICC repair after injury hold promise for future therapies.

Revised spectral metrics for body surface measurements of gastric electrophysiology

“…Cutaneous gastric myoelectrical recordings in controls commonly show transient high-amplitude bursts of low frequency noise (<2 cpm), occurring concurrently with stable gastric activity of normal frequency. 12 Normal gastric activity is globally entrained to frequencies near to 3 cpm, 32,33 hence these transient bursts likely reflect colonic activity, 20,34 or artifacts. 10,12 Dominant frequency metrics define the highest average power across the spectra and may therefore conflate low-frequency high-amplitude transients with gastric activity.…”

“…Pitfall 2: Conflation of low frequency transients with stable gastric activity Dominant frequency is typically calculated as the frequency associated with the highest power in the spectrum for a given period/window. This approach can be problematic, because normal cutaneous gastric myoelectrical recordings commonly show transient highamplitude bursts of low frequency noise (<2 cpm) occurring concurrently with stable gastric activity of normal frequency, 12 likely representing colonic activity, 20,21 or artifacts. 10,12 Dominant frequency calculations may therefore conflate non-gastric low frequency transients with stable gastric activity.…”

Long non-coding RNA MEG3 promotes tumor necrosis factor-alpha induced oxidative stress and apoptosis in interstitial cells of cajal via targeting the microRNA-21 /I-kappa-B-kinase beta axis

“…Interstitial Cells of Cajal (ICC) is a kind of pacemaker cells initially identified in the gastrointestinal tract, located in the myenteric region between nerve endings and smooth muscle cells [ 1 ]. Afterward, ICC has also been discovered in urogenital tissues, including ureter, prostate, and junction of renal pelvis and ureter, etc [ 2 , 3 ].…”

“…ICC and longitudinal smooth muscle cells have the same origin, mesenchymal stem/progenitor cells, which can become ICC under the stimulation of stem cell factor (SCF) during embryonic development. ICC plays a critical role in the peristaltic contractions of the gastrointestinal and urinary tract by generating a rhythmic depolarization and transmitting it to the musculature [ 1 , 4 ]. Recently, studies have proved that the dysfunction and loss of ICC are involved in hypokinetic disease, such as colonic motor dysfunction, gallstone and ureteropelvic junction obstruction (UPJO) [ 5–7 ].…”

Implantable, Transcutaneously Powered Neurostimulator System to Restore Gastrointestinal Motility

“…Although 4.4 million individuals in the United States suffer from constipation, it results in only 29 deaths per year (Digestive Disease Statistics, 1999). External electrical stimulation of impaired propulsive or segmental gastrointestinal motility may provide a successful long-term treatment of such disorders (Huizinga, 1986). It can also be extremely useful in shortening postoperative ileus (Livingston & Passaro, 1990), thus helping to significantly decrease postoperative hospitalization and reduce health-related costs.…”