Myogenic mechanism for peristalsis in the cat esophagus

A myogenic control system (MCS) is a fundamental determinant of peristalsis in the stomach, small bowel, and colon. In the esophagus, attention has focused on neuronal control, the potential for a MCS receiving less attention. The myogenic properties of the cat esophagus were studied in vitro with and without nerves blocked by 1 μM TTX. Muscle contraction was recorded, while electrical activity was monitored by suction electrodes. Spontaneous, nonperistaltic, electrical, and mechanical activity was seen in the longitudinal muscle and persisted after TTX. Spontaneous circular muscle activity was minimal, and peristalsis was not observed without pharmacological activation. Direct electrical stimulation (ES) in the presence of bethanechol or tetraethylammonium chloride (TEA) produced slow-wave oscillations and spike potentials accompanying smooth muscle contraction that progressed along the esophagus. Increased concentrations of either drug in the presence of TTX produced slow waves and spike discharges, accompanied by peristalsis in 5 of 8 TEA- and 2 of 11 bethanechol-stimulated preparations without ES. Depolarization of the muscle by increasing K+ concentration also produced slow waves but no peristalsis. We conclude that the MCS in the esophagus requires specific activation and is manifest by slow-wave oscillations of the membrane potential, which appear to be necessary, but are not sufficient for myogenic peristalsis. In vivo, additional control mechanisms are likely supplied by nerves.

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Waxing and waning of slow waves in intestinal musculature

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.250.1.g28 ◽

1986 ◽

Vol 250 (1) ◽

pp. G28-G34 ◽

Cited By ~ 5

Author(s):

N. Suzuki ◽

C. L. Prosser ◽

W. DeVos

Keyword(s):

Slow Wave ◽

Electrical Coupling ◽

Longitudinal Axis ◽

Slow Waves ◽

Rabbit Intestine ◽

Rabbit Small Intestine ◽

Intestinal Musculature ◽

Pattern Of Variation

Electrical slow waves from cat or rabbit small intestine show more variability when recorded in vivo than in vitro. One pattern of variation is waxing and waning of amplitude, or "spindling," during which two rhythms of slightly different frequency come in and out of phase. Fourier power analyses of slow waves during spindles show two frequency peaks of slow waves differing by 0.4-5.0 waves/min and corresponding to measured spindle durations of 12-150 s. Spindles can be induced in vitro in rabbit intestine by K depolarization of approximately 15 mV. Histograms of intracellular recordings of slow nonspindling waves show variation of 0.5-1.0 s on either side of a mean slow wave duration. Spindles are abolished by treatments that reduce electrical coupling between cells, e.g., hypertonic sucrose or lowered pH, but changes in calcium do not alter spindles. Simultaneous recordings by two electrodes in the longitudinal axis show synchrony of spindles at 2- to 3-mm but not at 5-mm separation and synchrony circumferentially to the opposite side of a segment. Contractions, both in vivo and in vitro, correspond with electrical spindles in amplitude. Spindle durations were significantly shorter in vivo than in vitro, indicating a significantly greater difference in vivo in the competing frequencies at the point of recording (P less than 0.01). Three conditions favoring waxing and waning are slight depolarization, variation in slow wave frequency at a point, and electrotonic coupling between muscle fibers. Spindles provide for rhythms of contractions of a 1- to 2-min period.

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Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00441.2006 ◽

2007 ◽

Vol 292 (4) ◽

pp. G1162-G1172 ◽

Cited By ~ 34

Author(s):

R. M. Gwynne ◽

J. C. Bornstein

Keyword(s):

Small Intestine ◽

Guinea Pig ◽

Motor Neurons ◽

Slow Wave ◽

Neural Circuit ◽

Circular Muscle ◽

Decanoic Acid ◽

Slow Waves ◽

Longitudinal Position

Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6–28.8 c/min, median 10.8 c/min; jejunum: 3.0–27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons.

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Relationship between transmural potential difference and smooth muscle slow waves and contractility in the rabbit small intestine in vitro

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y88-191 ◽

1988 ◽

Vol 66 (9) ◽

pp. 1161-1165 ◽

Cited By ~ 1

Author(s):

Beverley Greenwood ◽

Jan D. Huizinga ◽

Edwin Chow ◽

Wylie J. Dodds

Keyword(s):

Smooth Muscle ◽

Electrical Activity ◽

Slow Wave ◽

Muscle Activity ◽

Slow Waves ◽

Potential Difference ◽

Intraluminal Pressure ◽

Mechanical Activity ◽

Rabbit Ileum

The relationship between transmural potential difference (PD) and smooth muscle electrical and mechanical activity was investigated in the rabbit ileum in vitro. Transmural PD was monitored using agar salt bridge electrodes connected via calomel half cells to an electrometer. Force displacement transducers recorded predominantly longitudinal smooth muscle activity. Concurrently, predominantly circular muscle activity was recorded at three sites using intraluminal pressure probes. At the same sites, suction electrodes monitored electrical activity of the smooth muscle. In all experiments, fluctuations in transmural PD were temporally linked to smooth muscle mechanical and electrical activity. The frequency of PD oscillations, electrical slow waves, and cyclic pressure changes were identical within each segment. Adrenaline abolished smooth muscle electrical spiking, all mechanical activity, and transmural fluctuations in PD. However, the slow waves were not abolished, though their frequency was increased. Phentolamine but not propranolol reversed the effects of adrenaline, thus slow wave frequency is influenced by α-adrenergic stimulation in the rabbit ileum. In conclusion, oscillations in transmural PD are unrelated to the ionic processes associated with the slow wave. However, they are in some way linked to smooth muscle contractile activity, possibly via an intrinsic neural mechanism as observed in the guinea pig.

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Urokinase-derived peptides regulate vascular smooth muscle contraction in vitro and in vivo

The FASEB Journal ◽

10.1096/fj.14.10.1411 ◽

2000 ◽

Vol 14 (10) ◽

pp. 1411-1422 ◽

Cited By ~ 23

Author(s):

A. HAJ-YEHIA

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Muscle Contraction ◽

Smooth Muscle Contraction ◽

Vascular Smooth Muscle Contraction

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Cholinergic Switch between Two Types of Slow Waves in Cerebral Cortex

Cerebral Cortex ◽

10.1093/cercor/bhz320 ◽

2020 ◽

Vol 30 (6) ◽

pp. 3451-3466 ◽

Cited By ~ 4

Author(s):

Trang-Anh E Nghiem ◽

Núria Tort-Colet ◽

Tomasz Górski ◽

Ulisse Ferrari ◽

Shayan Moghimyfiroozabad ◽

...

Keyword(s):

Slow Wave ◽

Memory Consolidation ◽

Acetylcholine Receptors ◽

Computational Models ◽

Slow Wave Sleep ◽

Slow Waves ◽

Wave Dynamics ◽

Positive Effects

Abstract Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory versus excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.

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Potentiating TMEM16A channel function has no effect on airway goblet cells or bronchial and pulmonary vascular smooth muscle function

10.1101/2020.04.17.046177 ◽

2020 ◽

Author(s):

Henry Danahay ◽

Roy Fox ◽

Sarah Lilley ◽

Holly Charlton ◽

Kathryn Adley ◽

...

Keyword(s):

Smooth Muscle ◽

Muscle Contraction ◽

Goblet Cell ◽

Pulmonary Arteries ◽

Smooth Muscle Contraction ◽

Cell Numbers ◽

Channel Function ◽

Mucin Release

AbstractThe calcium-activated chloride channel TMEM16A enables chloride secretion across several transporting epithelia, including in the airway where it represents a therapeutic target for the treatment of cystic fibrosis. Additional roles for TMEM16A have also been proposed, including enhancing goblet cell exocytosis, increasing goblet cell numbers and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, both potentiation and inhibition, could affect any of these proposed biological roles.In vitro, a recently described potent and selective TMEM16A potentiator (ETX001) failed to stimulate mucin release from primary human bronchial epithelial (HBE) cells over a 24h exposure period using both biochemical and imaging endpoints. In addition, treatment of HBE cells with ETX001 or a potent and selective TMEM16A inhibitor (Ani9) for 4 days did not influence mucin release or goblet cell formation. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 driven goblet cell metaplasia model.Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats.Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.

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Studies in vivo and in vitro on effects of PGE2 on colonic motility in rabbits

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.262.1.g23 ◽

1992 ◽

Vol 262 (1) ◽

pp. G23-G29 ◽

Cited By ~ 4

Author(s):

R. Burakoff ◽

W. H. Percy

Keyword(s):

Colonic Motility ◽

Circular Muscle ◽

Distal Colon ◽

Muscle Layer ◽

Distal Region ◽

Mechanical Activity ◽

Experimental Conditions ◽

Motor Effects

Prostaglandins (PG) of the E series are synthesized throughout the gastrointestinal tract, and their elevated levels have been reported in many diarrheal states, including inflammatory bowel disease. It is already known that PGE2 has region-specific and muscle layer-specific effects in different areas of the intestine. The aim of this study was to evaluate possible dose-related motor effects of PGE2 on rabbit proximal and distal colon both in vivo and in vitro. We found that, in the proximal colon in vivo, PGE2 caused inhibition of myoelectric and mechanical activity at low doses but at higher doses caused marked excitation. Under the same experimental conditions, PGE2 caused only excitation in the distal colon, a phenomenon associated with an increase in antegrade contractions and diarrhea. In vitro, PGE2 caused excitation of both proximal and distal colonic longitudinal muscle and relaxation of the circular muscle. Its actions, however, were much more pronounced in the distal region. It is concluded that PGE2 has profound effects on colonic motility that are concentration dependent and that differ with the region of the colon under study. Furthermore, the evidence also suggests that elevated PGE2 levels in disease states may play a significant role in abnormal colonic motility and may facilitate the onset of diarrhea.

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Leukotriene D4 excitation of rabbit distal colon arises in the region of the muscularis mucosae

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.5.g753 ◽

1990 ◽

Vol 259 (5) ◽

pp. G753-G759

Author(s):

W. H. Percy ◽

S. Y. Lee ◽

M. B. Burton ◽

T. Tolentino ◽

R. Burakoff

Keyword(s):

Muscularis Propria ◽

Circular Muscle ◽

Distal Colon ◽

Muscle Layer ◽

Mechanical Activity ◽

Muscularis Mucosae ◽

Leukotriene D4 ◽

In Vitro Techniques

We previously have demonstrated in vivo that intra-arterial administration of leukotriene D4 (LTD4) causes increased myoelectric and mechanical activity in the rabbit distal colon. The aim of this study was to use both in vivo and in vitro techniques to try to elucidate the mechanism underlying this effect. In vivo the excitatory response of the rabbit distal colon to LTD4 was abolished by pretreatment with atropine (0.1 mg/kg iv) or hexamethonium (5 mg/kg iv) or the LTD4 receptor antagonist SK&F 102922 (0.8 micrograms/kg ia). In vitro neither the longitudinal nor the circular muscle layer responded to LTD4 (10(-10) to 10(-7) M) with a contractile response. Over the same concentration range, LTD4 caused contractions of the muscularis mucosae that were attenuated by either SK&F 102922 (10(-9) to 10(-7) M) or indomethacin (10(-6) M) but were unaffected by atropine (10(-6) M), pyrilamine (10(-6) M), or tetrodotoxin (10(-6) M). Full thickness segments of longitudinal muscle, circular muscle, and muscularis mucosae did not contract to LTD4. These data imply that LTD4-induced excitation of the rabbit distal colon in vivo arises as a result of the excitation of LTD4 receptors in the region of the muscularis mucosae and that this leads ultimately to the release of acetylcholine onto the muscularis propria. It is proposed that one possible mechanism leading to the latter effect is an increased excitability of intrinsic nerves resulting from a prostaglandin-induced depression of norepinephrine release from nerves impinging on the submucosal plexus.

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Effects of adlay hull extracts on uterine contraction and Ca2+ mobilization in the rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90367.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. E719-E726 ◽

Cited By ~ 18

Author(s):

Shih-Min Hsia ◽

Yueh-Hsiung Kuo ◽

Wenchang Chiang ◽

Paulus S. Wang

Keyword(s):

Smooth Muscle ◽

Muscle Contraction ◽

Uterine Contraction ◽

Smooth Muscle Contraction ◽

Uterine Contractions ◽

High K ◽

Intracellular Ca ◽

Feasible Alternative

Dysmenorrhea is directly related to elevated PGF2α levels. It is treated with nonsteroid antiinflammatory drugs (NSAIDs) in Western medicine. Since NSAIDs produce many side effects, Chinese medicinal therapy is considered as a feasible alternative medicine. Adlay ( Coix lachryma-jobi L. var. ma-yuen Stapf.) has been used as a traditional Chinese medicine for treating dysmenorrhea. However, the relationship between smooth muscle contraction and adlay extracts remains veiled. Therefore, we investigated this relationship in the rat uterus by measuring uterine contraction activity and recording the intrauterine pressure. We studied the in vivo and in vitro effects of the methanolic extracts of adlay hull (AHM) on uterine smooth muscle contraction. The extracts were fractionated using four different solvents: water, 1-butanol, ethyl acetate, and n-hexane; the four respective fractions were AHM-Wa, AHM-Bu, AHM-EA, and AHM-Hex. AHM-EA and its subfractions (175 μg/ml) inhibited uterine contractions induced by PGF2α, the Ca2+ channel activator Bay K 8644, and high K+ in a concentration-dependent manner in vitro. AHM-EA also inhibited PGF2α-induced uterine contractions in vivo; furthermore, 375 μg/ml of AHM-EA inhibited the Ca2+-dependent uterine contractions. Thus 375 μg/ml of AHM-EA consistently suppressed the increases in intracellular Ca2+ concentrations induced by PGF2α and high K+. We also demonstrated that naringenin and quercetin are the major pure chemical components of AHM-EA that inhibit PGF2α-induced uterine contractions. Thus AHM-EA probably inhibited uterine contraction by blocking external Ca2+ influx, leading to a decrease in intracellular Ca2+ concentration. Thus adlay hull may be considered as a feasible alternative therapeutic agent for dysmenorrhea.

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