Slow-wave potential

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A slow-wave potential is a rhythmic electrophysiological event in the gastrointestinal tract. The normal conduction of slow waves is one of the key regulators of gastrointestinal motility. [1] Slow waves are generated and propagated by a class of pacemaker cells called the interstitial cells of Cajal, which also act as intermediates between nerves and smooth muscle cells. [2] Slow waves generated in interstitial cells of Cajal spread to the surrounding smooth muscle cells and control motility.

Contents

Description

In the human enteric nervous system, the slow-wave threshold is the slow-wave potential which must be reached before a slow wave can be propagated in gut wall smooth muscle. Slow waves themselves seldom cause any smooth muscle contraction (Except for, probably in the stomach). When the amplitude of slow waves in smooth muscle cells reaches the slow-wave threshold — the L-type Ca2+ channels are activated, resulting in calcium influx and initiation of motility. [3] Slow waves are generated at unique intrinsic frequencies by the interstitial cells of Cajal, even within the same organ. Entrainment of these different intrinsic frequencies through electrical coupling allows these unique intrinsic frequencies to occur at a single frequency within the stomach and segments of the small intestine. Electron microscopic and dye coupling studies to date have confirmed gap junctions as the major coupling mechanisms between interstitial cells of Cajal. [4] [5]

Coupling between ICC and smooth muscle cells is uncertain. Gap junctions have been demonstrated in rare circumstances as one coupling mechanism between ICC and smooth muscle cells. [6] Another potential coupling mechanism is the "Peg and Socket" theory which demonstrates that the membranes of smooth muscle cells have the ability either form physical narrow "sockets" or "pegs" to lock onto other smooth muscle cells and/or interstitial cells of Cajal. [7]

Types

A depiction of a slow wave, contraction and electrical threshold in relation to smooth muscle tone and resting membrane potential. ElectricalThresholds.gif
A depiction of a slow wave, contraction and electrical threshold in relation to smooth muscle tone and resting membrane potential.

Gastric slow waves occur at around 3 cycles-per-minute in humans and exhibit significance variances in both amplitudes and propagation velocities in the stomach [8] [9] [10] due to the existence of a gradient of resting membrane potential gradient, [11] interstitial cells of Cajal distributions, and gastric wall thickness. Gastric slow waves frequency, propagation velocity, and amplitude demonstrate significant inter-species differences. Extracellular bioelectrical recording studies have demonstrated that gastric slow waves originate from a pacemaker region located on the greater curvature of the stomach. [8] [9] [10] Human gastric slow waves propagate slower in the corpus than in the pacemaker region and antrum of the stomach. [8] Up to four simultaneous slow wave wavefronts can occur in the human stomach.

Intestinal slow waves occur at around 12 cycles-per-minute in the duodenum, and decreases in frequency towards the colon. [12] [13] Entrainment of intestinal slow waves forms "frequency plateaus" in a piece-wise manner along the intestine. Similar to the stomach, intestinal slow waves frequency, propagation velocity, and amplitude also demonstrate significant inter-species differences.

In uterine smooth muscle, slow waves have not been consistently observed. Uterine muscle seems to generate action potentials spontaneously. [14]

In gastrointestinal smooth muscle, the slow-wave threshold can be altered by input from endogenous and exogenous innervation, as well as excitatory (acetylcholine and Substance P) and inhibitory (vasoactive intestinal peptide and nitric oxide) compounds. [15]

Related Research Articles

<span class="mw-page-title-main">Stomach</span> Digestive organ

The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach is involved in the gastric phase of digestion, following chewing. It performs a chemical breakdown by means of enzymes and hydrochloric acid.

<span class="mw-page-title-main">Gastrointestinal tract</span> Organ system within humans and other animals

The gastrointestinal tract is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and other animals, including the esophagus, stomach, and intestines. Food taken in through the mouth is digested to extract nutrients and absorb energy, and the waste expelled at the anus as feces. Gastrointestinal is an adjective meaning of or pertaining to the stomach and intestines.

<span class="mw-page-title-main">Peristalsis</span> Radially symmetrical contraction and relaxation of muscles

Peristalsis is a type of intestinal motility, characterized by radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, which is preceded by a simultaneous contraction of the longitudinal muscle and relaxation of the circular muscle in the lining of the gut.

<span class="mw-page-title-main">Enteric nervous system</span> Vital system controlling the gastrointestinal tract

The enteric nervous system (ENS) or intrinsic nervous system is one of the main divisions of the autonomic nervous system (ANS) and consists of a mesh-like system of neurons that governs the function of the gastrointestinal tract. It is capable of acting independently of the sympathetic and parasympathetic nervous systems, although it may be influenced by them. The ENS is nicknamed the "second brain". It is derived from neural crest cells.

<span class="mw-page-title-main">Enterochromaffin cell</span> Cell type

Enterochromaffin (EC) cells are a type of enteroendocrine cell, and neuroendocrine cell. They reside alongside the epithelium lining the lumen of the digestive tract and play a crucial role in gastrointestinal regulation, particularly intestinal motility and secretion. They were discovered by Nikolai Kulchitsky.

An electrogastrogram (EGG) is a computer generated graphic produced by electrogastrography, which detects, analyzes and records the myoelectrical signal generated by the movement of the smooth muscle of the stomach, intestines and other smooth muscle containing organs. An electrogastroenterogram or electroviscerogram is a similar display of the recording of myoelectrical activity of gastrointestinal or other organs which are able to generate myoelectrical activity.

<span class="mw-page-title-main">Interstitial cell of Cajal</span>

Interstitial cells of Cajal (ICC) are interstitial cells found in the gastrointestinal tract. There are different types of ICC with different functions. ICC and another type of interstitial cell, known as platelet-derived growth factor receptor alpha (PDGFRα) cells, are electrically coupled to smooth muscle cells via gap junctions, that work together as an SIP functional syncytium. Myenteric interstitial cells of Cajal (ICC-MY) serve as pacemaker cells that generate the bioelectrical events known as slow waves. Slow waves conduct to smooth muscle cells and cause phasic contractions.

<span class="mw-page-title-main">Intestinal pseudo-obstruction</span> Medical condition

Intestinal pseudo-obstruction (IPO) is a clinical syndrome caused by severe impairment in the ability of the intestines to push food through. It is characterized by the signs and symptoms of intestinal obstruction without any lesion in the intestinal lumen. Clinical features mimic those seen with mechanical intestinal obstructions and can include abdominal pain, nausea, abdominal distension, vomiting, dysphagia and constipation depending upon the part of the gastrointestinal tract involved.

<span class="mw-page-title-main">Vagovagal reflex</span>

Vagovagal reflex refers to gastrointestinal tract reflex circuits where afferent and efferent fibers of the vagus nerve coordinate responses to gut stimuli via the dorsal vagal complex in the brain. The vagovagal reflex controls contraction of the gastrointestinal muscle layers in response to distension of the tract by food. This reflex also allows for the accommodation of large amounts of food in the gastrointestinal tracts.

The enterogastric reflex is one of the three extrinsic reflexes of the gastrointestinal tract, the other two being the gastroileal reflex and the gastrocolic reflex. The enterogastric reflex is stimulated by duodenal distension. It can also be stimulated by a pH of 3-4 in the duodenum and by a pH of 1.5 in the stomach. Upon initiation of the reflex, the release of gastrin by G-cells in the antrum of the stomach is shut off. This in turn inhibits gastric motility and the secretion of gastric acid (HCl).

<span class="mw-page-title-main">Enteroendocrine cell</span>

Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota plays key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.

Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients and excrete waste products. The GI tract is composed of the alimentary canal, that runs from the mouth to the anus, as well as the associated glands, chemicals, hormones, and enzymes that assist in digestion. The major processes that occur in the GI tract are: motility, secretion, regulation, digestion and circulation. The proper function and coordination of these processes are vital for maintaining good health by providing for the effective digestion and uptake of nutrients.

<span class="mw-page-title-main">Motilin receptor</span> Protein-coding gene in the species Homo sapiens

Motilin receptor is a G protein-coupled receptor that binds motilin. It was first cloned in 1999 by Merck Laboratories. and scientists have since been searching for compounds to modify its behavior.

Gastroparesis, also called delayed gastric emptying, is a medical disorder consisting of weak muscular contractions (peristalsis) of the stomach, resulting in food and liquid remaining in the stomach for a prolonged period of time. Stomach contents thus exit more slowly into the duodenum of the digestive tract. This can result in irregular absorption of nutrients, inadequate nutrition, and poor glycemic control.

<span class="mw-page-title-main">CDX1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein CDX-1 is a protein in humans that is encoded by the CDX1 gene. CDX1 is expressed in the developing endoderm and its expression persists in the intestine throughout adulthood. CDX1 protein expression varies along the intestine, with high expression in intestinal crypts and diminishing expression along intestinal villi.

The basal or basic electrical rhythm (BER) or electrical control activity (ECA) is the spontaneous depolarization and repolarization of pacemaker cells known as interstitial cells of Cajal (ICCs) in the smooth muscle of the stomach, small intestine, and large intestine. This electrical rhythm is spread through gap junctions in the smooth muscle of the GI tract. These pacemaker cells, also called the ICCs, control the frequency of contractions in the gastrointestinal tract. The cells can be located in either the circular or longitudinal layer of the smooth muscle in the GI tract; circular for the small and large intestine, longitudinal for the stomach. The frequency of contraction differs at each location in the GI tract beginning with 3 per minute in the stomach, then 12 per minute in the duodenum, 9 per minute in the ileum, and a normally low one contraction per 30 minutes in the large intestines that increases 3 to 4 times a day due to a phenomenon called mass movement. The basal electrical rhythm controls the frequency of contraction but additional neuronal and hormonal controls regulate the strength of each contraction.

<span class="mw-page-title-main">ANO1</span> Protein-coding gene in the species Homo sapiens

Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a protein that, in humans, is encoded by the ANO1 gene. Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel and a bicarbonate channel. additionally Anoctamin-1 is apical iodide channel. It is expressed in smooth muscle, epithelial cells, vomeronasal neurons, olfactory sustentacular cells, and is highly expressed in interstitial cells of Cajal (ICC) throughout the gastrointestinal tract.

A prokinetic agent is a type of drug which enhances gastrointestinal motility by increasing the frequency or strength of contractions, but without disrupting their rhythm. They are used to treat certain gastrointestinal symptoms, including abdominal discomfort, bloating, constipation, heart burn, nausea, and vomiting; and certain gastrointestinal disorders, including irritable bowel syndrome, gastritis, gastroparesis, and functional dyspepsia.

<span class="mw-page-title-main">Gastrointestinal wall</span> Digestive system structure

The gastrointestinal wall of the gastrointestinal tract is made up of four layers of specialised tissue. From the inner cavity of the gut outwards, these are:

  1. Mucosa
  2. Submucosa
  3. Muscular layer
  4. Serosa or adventitia
<span class="mw-page-title-main">Human digestive system</span> Digestive system in humans

The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion. Digestion involves the breakdown of food into smaller and smaller components, until they can be absorbed and assimilated into the body. The process of digestion has three stages: the cephalic phase, the gastric phase, and the intestinal phase.

References

  1. ↑ Huizinga, J. D.; Lammers, W. J. E. P. (2008). "Gut peristalsis is governed by a multitude of cooperating mechanisms". AJP: Gastrointestinal and Liver Physiology. 296 (1): G1–8. doi:10.1152/ajpgi.90380.2008. PMID   18988693.
  2. ↑ Hanani, Menachem; Farrugia, Gianrico; Komuro, Terumasa (2004). Intercellular Coupling of Interstitial Cells of Cajal in the Digestive Tract. International Review of Cytology. Vol. 242. pp. 249–82. doi:10.1016/S0074-7696(04)42006-3. ISBN   978-0-12-364646-0. PMID   15598471.
  3. ↑ Thorneloe, Kevin S.; Nelson, Mark T. (2005). "Ion channels in smooth muscle: Regulators of intracellular calcium and contractility". Canadian Journal of Physiology and Pharmacology. 83 (3): 215–42. doi:10.1139/y05-016. PMID   15870837.
  4. ↑ Horiguchi, K; Komuro, T (1998). "Ultrastructural characterization of interstitial cells of Cajal in the rat small intestine using control and Ws/Ws mutant rats". Cell and Tissue Research. 293 (2): 277–84. doi:10.1007/s004410051119. PMID   9662650. S2CID   26179257.
  5. ↑ Zamir, O.; Hanani, M. (1990). "Intercellular dye-coupling in intestinal smooth muscle. Are gap junctions required for intercellular coupling?". Experientia. 46 (10): 1002–5. doi:10.1007/BF01940654. PMID   2226711. S2CID   30692665.
  6. ↑ Ishikawa, Koichi; Komuro, Terumasa (1996). "Characterization of the interstitial cells associated with the submuscular plexus of the guinea-pig colon". Anatomy and Embryology. 194 (1): 49–55. doi:10.1007/BF00196314. PMID   8800422. S2CID   23410156.
  7. ↑ Thuneberg, Lars; Peters, Susan (2001). "Toward a concept of stretch-coupling in smooth muscle. I. Anatomy of intestinal segmentation and sleeve contractions". The Anatomical Record. 262 (1): 110–24. doi:10.1002/1097-0185(20010101)262:1<110::AID-AR1016>3.0.CO;2-0. PMID   11146434. S2CID   34906117.
  8. 1 2 3 O'Grady, G.; Du, P.; Cheng, L. K.; Egbuji, J. U.; Lammers, W. J. E. P.; Windsor, J. A.; Pullan, A. J. (2010). "Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping". AJP: Gastrointestinal and Liver Physiology. 299 (3): G585–92. doi:10.1152/ajpgi.00125.2010. PMC   2950696 . PMID   20595620.
  9. 1 2 Egbuji, J. U.; o’Grady, G.; Du, P.; Cheng, L. K.; Lammers, W. J. E. P.; Windsor, J. A.; Pullan, A. J. (2010). "Origin, propagation and regional characteristics of porcine gastric slow wave activity determined by high-resolution mapping". Neurogastroenterology & Motility. 22 (10): e292–300. doi:10.1111/j.1365-2982.2010.01538.x. PMC   4110485 . PMID   20618830.
  10. 1 2 Lammers, W. J. E. P.; Ver Donck, L.; Stephen, B.; Smets, D.; Schuurkes, J. A. J. (2009). "Origin and propagation of the slow wave in the canine stomach: The outlines of a gastric conduction system". AJP: Gastrointestinal and Liver Physiology. 296 (6): G1200–10. doi:10.1152/ajpgi.90581.2008. PMID   19359425.
  11. ↑ Farrugia, G.; Lei, S.; Lin, X.; Miller, S. M.; Nath, K. A.; Ferris, C. D.; Levitt, M.; Szurszewski, J. H. (2003). "A major role for carbon monoxide as an endogenous hyperpolarizing factor in the gastrointestinal tract". Proceedings of the National Academy of Sciences. 100 (14): 8567–70. Bibcode:2003PNAS..100.8567F. doi: 10.1073/pnas.1431233100 . PMC   166269 . PMID   12832617.
  12. ↑ Angeli, Timothy R; O'Grady, Gregory; Paskaranandavadivel, Niranchan; Erickson, Jonathan C; Du, Peng; Pullan, Andrew J; Bissett, Ian P; Cheng, Leo K (2013). "Experimental and Automated Analysis Techniques for High-resolution Electrical Mapping of Small Intestine Slow Wave Activity". Journal of Neurogastroenterology and Motility. 19 (2): 179–91. doi:10.5056/jnm.2013.19.2.179. PMC   3644654 . PMID   23667749.
  13. ↑ Lammers, W. J. E. P.; Stephen, B. (2007). "Origin and propagation of individual slow waves along the intact feline small intestine". Experimental Physiology. 93 (3): 334–46. doi: 10.1113/expphysiol.2007.039180 . PMID   18156170.
  14. ↑ Aguilar, H. N.; Mitchell, B. F. (2010). "Physiological pathways and molecular mechanisms regulating uterine contractility". Human Reproduction Update. 16 (6): 725–44. doi: 10.1093/humupd/dmq016 . PMID   20551073.
  15. ↑ Pathophysiology. Porth. 7th Ed. pg.875–878

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