Spatiotemporal electrical and motility mapping of distension-induced propagating oscillations in the murine small intestine
T. C. Seerden,1
W. J. E. P. Lammers,2
B. Y. De Winter,1
J. G. De Man,1 and
P. A. Pelckmans1
1Division of Gastroenterology, University of Antwerp, Wilrijk, Belgium; and 2Department of Physiology, United Arab Emirates University, Al Ain, United Arab Emirates
Submitted 3 May 2005
; accepted in final form 3 August 2005
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ABSTRACT
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Since the development of knockout animals, the mouse has become an important model to study gastrointestinal motility. However, little information is available on the electrical and contractile activities induced by distension in the murine small intestine. Spatiotemporal electrical mapping and mechanical recordings were made from isolated intestinal segments from different regions of the murine small intestine during distension. The electrical activity was recorded with 16 extracellular electrodes while motility was assessed simultaneously by tracking the border movements with a digital camera. Distension induced propagating oscillatory contractions in isolated intestinal segments. These propagating contractions were dictated by the underlying propagating slow wave with superimposed spikes. The frequencies, velocities, and direction of the propagating oscillations strongly correlated with the frequencies (r = 0.86), velocities (r = 0.84), and direction (r = 1) of the electrical slow waves. N
-nitro-L-arginine methyl ester decreased the maximal diameter of the segment and reduced the peak contraction amplitude of the propagating oscillatory contractions, whereas atropine and verapamil blocked the propagating oscillations. Tetrodotoxin had little effect on the maximal diameter and peak contraction amplitude. In conclusion, distension in the murine small intestine does not initiate peristaltic reflexes but induces a propagating oscillatory motor pattern that is determined by propagating slow waves with superimposed spikes. These spikes are cholinergic and calcium dependent.
slow wave; spike; enteric nervous system; small intestine; mice; peristalsis
THE SMALL INTESTINE produces a variety of motility patterns to ensure appropriate mixing and propulsion of contents during absorption, digestion, and excretion of food (6, 21). These organized motility patterns are the result of cooperation between smooth muscle cells, interstitial cells of Cajal, and enteric nerves (13). Several patterns of motility have been described such as peristaltic contractions (11, 26), segmental contractions (9, 10), and pendular movements (20, 25). Most studies have focused on the peristaltic contractions of the guinea pig small intestine using an in vitro modified Trendelenburg setup (23, 27). Only a few studies have investigated other motor patterns (10, 25).
Since the development of knockout animals, the mouse has become an important model to study gastrointestinal motility. Genetically modified animals offer an additional approach to the pharmacological study of characterizing the receptors involved in the motor function of the gut (1, 3). It is therefore of importance to describe normal murine gastrointestinal motor patterns.
In recent years, high-resolution spatiotemporal motility and electrical mapping have been introduced in gastrointestinal research (11, 16, 17). In this study, we used high-resolution spatiotemporal electrical and motility mapping to simultaneously study electrical and motor activities in different regions of the murine small intestine before and during distension.
We found that, in contrast to motility behavior in other animals, distension does not induce peristaltic contraction in the small intestine of mice. Instead, sigmoidal or oscillatory contractions that propagated in the oral or aboral direction occurred. Electrical recordings showed that these propagating oscillations were dictated by the timing and direction of propagation of underlying slow waves with accompanying action potentials.
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METHODS
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All experimental procedures were approved by the Animal Research Ethical Committee at the United Arab Emirates University. After an overnight fast, male mice (average weight: 30 g) were anesthetized with diethyl ether and killed by exsanguination. The small intestine was exposed by a midline abdominal incision, rapidly removed, and placed in cold aerated Tyrode solution [containing (in mM) 130 NaCl, 4.5 KCl, 2.2 CaCl2, 0.6 MgCl2, 24.2 NaHCO3, 1.2 NaH2PO4, and 11 glucose]. The small intestine was gently flushed, and, subsequently, segments (length: 2.53.5 cm) of the duodenum, jejunum, proximal ileum, or distal ileum were prepared. The duodenal segments were taken 0.5 cm distal to the pyloric sphincter, the jejunal segments 1 cm postligament of Treitz, and the proximal and distal ileum segments, respectively, 10 and 1 cm proximal to the ileocolic junction.
After preparation, the intestinal segments were mounted in a 45-ml organ bath and superfused with a modified Tyrode solution (100 ml/min) that was saturated with 95% O2-5% CO2 and kept at 37 ± 0.5°C. The oral side of the intestinal segment was connected to a perfusion pump (inflow: 0.150.5 ml/min). The distal side was connected to a tube, the outlet of which could be increased in height (Fig. 1A). Soot markers were placed on the serosal surface of the segment (16). A digital video recorder was positioned in front of the organ bath, and a row of 16 extracellular electrodes was gently put on the serosa of the intestinal segment. After a 30-min equilibration period, propagating oscillations of the intestinal segments were elicited by luminal perfusion against an aboral pressure of 2.53.0 cmH2O. The electrical and motor activities of these oscillations were mapped with the extracellular electrodes and the digital video camera, respectively.

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Fig. 1. A: diagram of the experimental setup. An isolated murine jejunal segment is connected to an inlet (infusion rate: 0.15 ml/min) and an outlet that can be raised to 2 cm to induce distension. An array of 16 extracellular electrodes and a digital video camera record the electrical and motility activities, respectively. B: snapshot of one frame of the video recording indicating the border analysis performed. An area of interest, indicated by the white rectangle, is selected spanning the intestinal border at the contralateral side of the electrode array. After the threshold value is set, the program determines the location of the border in the area of interest at 32 positions (white dots). C: movement of each dot in time. Dot 1 is located at the oral end, and dot 32 is located at the aboral end. Circular contraction occurs when the dots move upwards. The vertical line indicates the timing of the snapshot.
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Electrical activities were recorded with a single longitudinal row of 16 extracellular unipolar AgCl2 electrodes (Teflon-coated silver wires; 0.3 mm interelectrode distance; 5.5 mm total distance; Fig. 1). The electrodes were connected to 16 alternating-current preamplifiers (gain: 4,000), where the signals were subsequently filtered (2400 Hz), digitized (8 bits, 1 kHz sampling rate/channel), transferred to a personal computer, digitally filtered (20-point running average), and displayed on screen. After the experiments, the recorded electrical signals were further analyzed with Smoothmap software (custom developed, written in Delphi) (17).
Motility recordings were performed with a digital video camera (Sony DCR-TRV 10 E; Fig. 1). After the experiments, periods of interest were transferred by IEEE 1394 (firewire) to a Mac G4 (Apple) using a commercial software package (iMovie, Apple). For analysis, the video files were converted at 25 frames/s (40-ms interframe interval, Quicktime). After conversion, all frames were sequentially analyzed using a custom-made software package (Motilitymap 1.3 software, written in Real Basic 5.0) (16). An area of interest, as indicated by the white rectangle in Fig. 1B, was selected spanning the intestinal border at the contralateral side of the electrode array. After the threshold value was set, the program determined, frame by frame, the location of the border at 32 positions (white dots in Fig. 1, B and C). In addition, the movements of the soot markers were tracked to determine longitudinal contractions (15).
In the first series of experiments (n = 21), the electrical and motility activities of the propagating oscillations were simultaneously recorded during distension periods of 13 min. To synchronize the electrograms with the video signals, a digital stimulator (Neuro Data PG 4000) produced rhythmic pulses that were fed into one of the amplifiers and converted in an auditory signal that was recorded by the video camera. In the second set of experiments (n = 16), we performed pharmacological studies. When the preparations produced propagating oscillatory contractions during distension, tetrodotxin (TTX; 3 x 106 M), atropine (106 M), verapamil (105 M), and N
-nitro-L-arginine methyl ester (L-NAME; 3 x 104 M) were added to the circulating Tyrode solution. Two 1-min recordings were made: the first just before the addition of the drug and the second 5 min after drug administration.
Oscillation contractions and slow wave frequencies are expressed as cycles per minute. Conduction velocities of the slow wave and oscillations are presented as centimeters per second. The peak contraction amplitude was calculated by the following equation: [1 (minimum diameter/maximal diameter)] x 100 and expressed as the percent reduction in intestinal diameter. All data are shown as means ± SD, and n refers to the number of animals from which the data were obtained.
TTX, verapamil, L-NAME, and atropine were purchased from Sigma-Aldrich (St. Louis, MO), dissolved in distilled water, and added to the tissue bath Tyrode solution.
All data were analyzed with SPSS 11.0 for Windows software (SPSS; Chicago, IL) and Graphpad Prism 4 software (GraphPad Software; San Diego, CA). Paired data were compared using paired Student's t-test. Unpaired data were analyzed using ANOVA as appropriate. P values of <0.05 were considered to be significant. For the correlation studies, data from motility mapping were combined with the results of the electrical recordings, and Spearman correlation coefficients (R) were determined. P values of <0.01 were considered to be significant.
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RESULTS
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At 0 cmH2O of intraluminal pressure, the isolated murine small intestine showed strong pendular movements in the longitudinal direction with few or no circular contractions (Fig. 2, left). When the outlet was raised to 2 cmH2O (Fig. 1), the segment became distended, and circular contractions occurred at the same rhythm as the continuing pendular contractions (Fig. 2, middle). When the outlet was returned to 0 cmH2O of pressure, the circular contractions, but not the longitudinal contractions, immediately stopped (Fig. 2, right). The series of snapshots taken during such an event shown in Fig. 3 highlights the circular contractile activity during distension. This is further presented at a high resolution and for a longer period of time in Fig. 4, together with the simultaneously recorded electrical activities.

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Fig. 2. At 0 cmH2O of pressure, the isolated jejunal segment generated strong rhythmic (pendular) longitudinal contractions and very weak irregular circular contractions (left). After a step increase of the intraluminal pressure to 2 cmH2O, regular circular contractions were immediately induced while the pendular contractions continued (middle). When the intraluminal pressure was decreased back to resting level (0 cmH2O; right), the propagating circular contractility immediately disappeared without a major change in longitudinal contractions. The circle in the left snapshot indicates the location of the soot marker that was tracked to generate the longitudinal tracing.
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Fig. 3. Sequential snapshots of an isolated murine duodenum before and during distension. Before distension, there was hardly any movement of the selected border in this period of 2 s, whereas during distension, the border showed considerable circular movements. The electrical and motility traces of this experiment are shown in Fig. 4.
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Fig. 4. Plot of the electrical and motility activities before and during distension in an isolated segment from the murine duodenum. A and C: electrical signals. B and D: motility traces. The timings of the snapshots in Fig. 3 are indicated below the motility traces (arrows, 0.02.0 s). Before distension, the slow wave (SW) propagated uniformly in the oral direction, whereas the motility traces showed hardly any movements. During distension, the slow waves continued to propagate in the same pattern with the emergence of spikes in most leads and during every slow wave cycle. At the same time, motility traces showed rhythmic oscillations that propagated in the same direction as the slow waves. Dashed lines in C and D indicate the appearance of the first slow wave in the segment at electrode 16. The arrow in D represents the timing and direction of the slow wave propagation as shown in C and indicates that the slow wave propagates while the segment is relaxing from the previous contraction.
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Figure 4, A and B, shows the situation before distension. Four slow waves propagated, in this case, in the oral direction, followed by little or no action potentials (spikes). The border of the segment showed hardly any mechanical activity in the circular direction (Fig. 4B). Upon distension (Fig. 4, C and D), the slow waves continued to propagate in the oral direction but were now followed by several large-amplitude spikes. These spikes occurred in practically all leads, spanning the length of the segment, and occurred after every slow wave. At the same time, the border of the segment showed oscillatory contractions (Fig. 4D). Moreover, these oscillatory contractions did not occur simultaneously along the length of the segment but occurred earlier in the distal part and later in the oral part. The arrow in Fig. 4D shows that the slow wave propagated while the tissue was relaxing from a previous circular contraction. It is also clear that the contraction, followed by the relaxation, occurred in the same direction as the slow wave. Both the spikes and contractions are also linked in time to the slow waves. In this example, the spikes started to occur 274 (±61 SD) ms after the slow wave, whereas the contraction began 698 (±57 SD) ms after the slow waves, as measured at each site.
Similar results were obtained from segments originating from all parts of the murine small intestine. Figure 5 shows examples obtained from the duodenum, jejunum, and proximal and distal ileum during distension. Figure 5 shows propagating slow waves followed by spiking activity (top) and propagating oscillations (bottom). Moreover, the direction of the circular contraction always followed that of the slow wave, as indicated by the parallelism of the slow wave arrow (arrows) and the onset of the circular contraction (dashed arrows). This was irrespective of whether the slow wave was propagating in the aboral direction (Fig. 5, left and middle left) or in the oral direction (Fig. 5, right middle and right).

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Fig. 5. Examples of distension-induced propagating oscillations (PO) as recorded in segments isolated from the duodenum, jejunum, and proximal and distal ileum. Top: electrical signals. Bottom: motility traces. Arrows are drawn in the electrical traces as determined by the timing and direction of slow wave propagation and are superposed onto the motility traces, indicating that slow wave propagation occurs during the previous relaxation. Dashed arrows indicate the onset of the following contraction and show that contraction propagates in the same direction as the preceding slow wave.
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Table 1 summarizes the electrical and mechanical activities measured in 21 segments from different parts of the murine small intestine upon distension. There were no statistical differences at any level in the intestine between the slow wave frequencies and the oscillation frequencies or in their velocities of propagation. There was, however, a slight but significant decrease in slow wave frequency down the intestine, and the same gradient was found with the frequency of contraction. Figure 6 plots the correlation coefficients between the electrical and mechanical velocities (left; r = 0.84, P < 0.001) and electrical and mechanical frequencies (right; r = 0.86, P < 0.001). In addition, there was a 1:1 correlation between the direction of slow wave propagation and that of the circular contraction.
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Table 1. Slow wave and oscillation frequencies and velocities in the murine duodenum, jejunum, and proximal and distal ileum
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Fig. 6. A: conduction velocity of the propagating oscillation against that of the underlying slow wave conduction velocity. B: oscillation frequency against the underlying slow wave frequency. In both cases, strong significant correlations were found.
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This linkage between slow waves and circular contractions was not always constant, and occasionally other rhythms could be observed. An example of this is shown in Fig. 7. In this recording, which lasted for
18 s, the slow waves propagated uniformly in the aboral direction. Spiking activity, however, was not uniform throughout this period. Instead, a pattern of migrating bursts could be seen in a cycle of about three to four slow waves. During the first slow wave, spike bursts occurred along the eight to nine oral electrodes. During the second slow wave, all electrodes showed spike bursts, whereas during the third slow wave, only the distal 810 electrodes showed spikes. This pattern was faithfully reproduced by the circular contractions as shown in the motility traces (Fig. 7B; group of three arrows). Furthermore, this pattern repeated itself several times during the time course of this recording (groups 24). In summary, despite a constant propagation of the slow wave throughout this period, the propagation of the circular contraction was not continuous as it was also dictated by an alternating pattern of spiking activity.

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Fig. 7. Rhythmic spike discharges and corresponding motility in an isolated murine duodenum. In this 18-s record, a rhythmic pattern of spiking discharge was identified following regular aborally propagating slow waves (first and last arrow in A). In this pattern, spikes occurred first predominantly in oral leads, followed in the next slow wave by spikes that occurred over the whole length, whereas after the third slow wave spikes occurred predominantly in aboral leads. This rhythm was repeated three times (groups 24) during this 30-s record. The motility traces (B) followed this spiking rhythm (dashed box). The three arrows drawn in the motility traces indicate the three individual contraction components of this rhythm.
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The linkage between slow waves and spikes and between spikes and circular contractions was also tested by the addition of several drugs: verapamil, TTX, atropine, and L-NAME (Fig. 8).

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Fig. 8. Effects of verapamil, tetrodotoxin (TTX), atropine, and N -nitro-L-arginine methyl ester (L-NAME) on distension-induced propagating oscillations. Top: snapshots of the preparations. Middle: electrical activities. Bottom: corresponding motility. The control distended preparation shows accompanying electrical and mechanical activities before the addition of verapamil. Verapamil and atropine abolished all spikes and contractions, leaving the segment distended (4.4 and 3.2 mm, respectively). TTX did not affect slow waves, spikes, or motility. L-NAME did not abolish spiking activity upon distension but failed to relax the tissue, leaving the segment relatively constricted.
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Verapamil totally blocked all longitudinal and circular contractile activity in all preparations, and this resulted in an immobile atonic segment. The maximal diameter increased significantly, and the peak contraction amplitude became zero. In the electrical recordings, all spiking activity disappeared, and, in three of the four preparations, no slow waves could be visualized either.
L-NAME did not affect slow waves and spiking activities, but the segments failed to relax, leading to a decrease in the peak contraction amplitude of the propagating oscillations and a decrease in the width of the intestinal segment (Table 2).
Atropine inhibited spiking activities but not the slow waves. The propagating oscillations stopped, and only weak pendular contractions were found. Concomitantly, the maximal diameter increased, and the peak contraction amplitude dramatically decreased (Table 2).
TTX essentially had little effect and did not abolish slow waves, action potentials, or propagating oscillations. The maximal diameter of the segment and the peak amplitude of the propagating oscillation were unchanged after the addition of TTX (Table 2).
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DISCUSSION
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In contrast to the situation in other species (26), distension of a segment of the murine small intestine does not induce the stereotypical pattern of propagating peristaltic contraction (peristaltic reflex) that is observed in the small intestine of the guinea pig (22). Instead, distension of the murine small intestine evoked a pattern of oscillatory contractions that differs from the peristaltic contractions in that the contractions can propagate in either the oral or aboral direction (Figs. 4, 5, and 7), whereas peristaltic contractions always propagate aborally (2). The reasons why peristaltic contractions do not occur in the murine small intestine are not clear. Possibly, differences in the architecture or behavior of the enteric nervous system underlie the absence of the peristaltic motor pattern in the murine small intestine.
Huizinga and colleagues (7, 12) have also studied the isolated murine small intestine during distension. They recorded from three individual suction electrodes and from three intraluminal pressure ports while monitoring the outflow (7, 12). Upon distension, the number of action potentials coupled to the slow waves increased, which led to an increase in intraluminal pressure and an increase in outflow (7). Our results are comparable with their findings. Furthermore, because of our higher resolution, we could better determine the direction of the slow wave propagation and correlate this with the behavior of the intestinal wall. They also reported the occurrence of burst-type activities upon distension, which is probably the same as the cyclic activity we analyzed in Fig. 7.
The present findings lead us to propose the following model of propagating oscillations, shown in Fig. 9. In the nondistended murine segment, slow waves occur with little or no circular spikes (Fig. 9A). Upon distension, the diameter of the segment increases, which, in turn, induces the appearance of action potentials (Fig. 9B). These spikes, localized as they are in a limited area after the upstroke of the slow wave, induce contraction in that location but not in adjacent areas (Fig. 9C). Because the slow wave propagates, the area where the spikes occur follows, and, hence, the resulting contraction.

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Fig. 9. Mechanism of distension-induced propagating oscillations in the murine small intestine. AD: diagram of the electrical activity in a tubular segment. Upon distension (B), spikes are evoked, which will induce localized contractions (C). As the slow wave propagates (D), it is followed by spikes and, therefore, by the local contraction.
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A distinction must be made between the contractions of the longitudinal and circular layer. Longitudinal contractions, also called pendular contractions (11, 20) or sleeve contractions (25), occur in the presence or absence of distension (Fig. 2). They also occur at the same rhythm of the slow wave and are likely induced by spikes occurring in the longitudinal layer (15). The propagating contractions investigated in this study are caused by distension-induced circular spikes that contract the circular muscle layer in the transversal direction. As these spikes often occurred after every slow wave, the contraction pattern resembles a series of oscillations. In short, pendular contractions and propagating oscillations are independent of each other in their mode of induction but share the same frequency as both are driven by the same slow wave.
As shown in Figs. 2 and 7, these patterns of contractions are not always constant and can easily wax and wane. In the case of propagating oscillations, this is determined by whether or not circular spikes follow the slow waves (Fig. 7). Pendular contractions may also vary (Fig. 2), depending on the occurrence of longitudinal spikes but also, as recently shown, by the pattern of propagation of the slow wave (15).
The relationship between slow waves and propagating oscillations is present along the length of the small intestine. As in other species, there was a frequency gradient along the small intestine in mice. The small but significant drop in slow wave frequency down the intestine was faithfully mirrored by an equal reduction in frequencies of the contractions (Table 1).
The pharmacological studies confirmed the mechanism of propagating oscillations presented here. Verapamil abolished the initiation of all spikes and reduced the segment into a distended inert tube. As in intact segments from the cat small intestine, verapamil also reduced slow wave activity (19). Atropine inhibited the distension-induced spiking activity and thereby blocked the propagating oscillations. This suggests that cholinergic pathways are involved in the generation of propagating oscillations.
Because L-NAME blocks endogenous nitric oxide release (5) and thus increases tonus of smooth muscle cells, the diameter of all preparations significantly decreased. The relaxation after the contraction was hampered, and the amplitude of the propagating oscillation during distension was reduced; however, slow wave and spike activity were not affected.
In the presence of TTX, action potentials superimposed on slow waves were not abolished, and, therefore, propagating oscillations with a similar frequency and conduction velocity as before the drug application continued. From these results, we can conclude that despite a blockade of neural activity, the propagating oscillations can occur by smooth muscle excitation (12). Excitation of intestinal smooth muscle cells by TTX is a well-documented phenomena already described in the 1970s by Bortoff and Muller (4) and Wood (28). They hypothesized that the blockade of the tonically released inhibitory neurotransmitters by TTX in isolated segments in vitro increased the excitability of the circular muscle layer to mechanical stimulation. In summary, these results suggest the involvement of L-type calcium channels and cholinergic and nitrergic pathways in the propagating oscillations of the murine small intestine.
This is the first time that oscillatory contractions have been reported in the gastrointestinal system of the mouse. In other systems, oscillatory contractions also occur and have been described and simulated (8). It would be of interest to determine how the propulsive effect of this type of contraction relates to that of other motor patterns, such as peristaltic (14, 18) or pendular contractions (20). The fact that the direction of the slow wave dictates the direction of the oscillatory contraction may complicate matters because the direction of the slow wave conduction frequently changes in isolated segments of the murine small intestine.
It should be kept in mind that the type of peristalsis studied here is determined and limited by the methodology used. The study was performed in an isolated segment and stimulated by fluid distension and not, for example, by a bolus or local distension (2, 24).
In conclusion, distension in the mouse small intestine does not induce a peristaltic reflex but a segmental pattern of contraction. These propagating oscillations, a term we propose based on their behavior and pattern, are dictated by the propagating slow wave and occurrence of circular spikes. They occur in all parts of the small intestine, can migrate both orally and aborally, and can be modified by pharmacological tools.
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GRANTS
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This study was supported by the Faculty of Medicine and Health Sciences, United Arab Emirates University, by an IWT fellowship (no. 23274) from the Flemish Government (to T. C. Seerden) and by Belgian Interuniversity Pole of Attraction Programme Grant nr P5/20 (Services of the Prime Minister, Federal Services for Scientific, Technical and Cultural Affairs).
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ACKNOWLEDGMENTS
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The authors acknowledge the work of D. Dhanasekaran, who constructed the 16-electrode array, and B. Stephen, for the experimental assistance.
Part of this work was presented at the 12th European Neurogastroenterology and Motility meeting in Cambridge, United Kingdom, in 2004.
Examples of propagating oscillations are available as movies at http://www.smoothmap.org.
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FOOTNOTES
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Address for reprint requests and other correspondence: W. J. E. P. Lammers, Dept. of Physiology, United Arab Emirates Univ., PO 17666, Al Ain, United Arab Emirates (e-mail: wlammers{at}smoothmap.org)
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES
|
---|
- Abdu F, Hicks GA, Hennig G, Allen JP, and Grundy D. Somatostatin sst2 receptors inhibit peristalsis in the rat and mouse jejunum. Am J Physiol Gastrointest Liver Physiol 282: G624G633, 2002.[Abstract/Free Full Text]
- Bayliss WM and Starling EH. The movements and innervation of the small intestine. J Physiol 24: 99143, 1899.
- Bian X, Ren J, DeVries M, Schnegelsberg B, Cockayne DA, Ford AP, and Galligan JJ. Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit. J Physiol 551: 309322, 2003.[Abstract/Free Full Text]
- Bortoff A and Muller R. Stimulation of intestinal smooth muscle by atropine, procaine, and tetrodotoxin. Am J Physiol 229: 16091613, 1975.[Abstract/Free Full Text]
- Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, and Herman AG. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 345: 346347, 1990.[CrossRef][ISI][Medline]
- Costa M, Brookes SJ, and Hennig GW. Anatomy and physiology of the enteric nervous system. Gut 47, Suppl 4: iv15iv19, 2000.
- Der-Silaphet T, Malysz J, Hagel S, Larry AA, and Huizinga JD. Interstitial cells of cajal direct normal propulsive contractile activity in the mouse small intestine. Gastroenterology 114: 724736, 1998.[ISI][Medline]
- Eytan O, Jaffa AJ, and Elad D. Peristaltic flow in a tapered channel: application to embryo transport within the uterine cavity. Med Eng Phys 23: 473482, 2001.[ISI][Medline]
- Grivel ML and Ruckebusch Y. The propagation of segmental contractions along the small intestine. J Physiol 227: 611625, 1972.[ISI][Medline]
- Gwynne RM, Thomas EA, Goh SM, Sjovall H, and Bornstein JC. Segmentation induced by intraluminal fatty acid in isolated guinea-pig duodenum and jejunum. J Physiol 556: 557569, 2004.[Abstract/Free Full Text]
- Hennig GW, Costa M, Chen BN, and Brookes SJ. Quantitative analysis of peristalsis in the guinea-pig small intestine using spatio-temporal maps. J Physiol 517: 575590, 1999.[Abstract/Free Full Text]
- Huizinga JD, Ambrous K, and Der-Silaphet T. Co-operation between neural and myogenic mechanisms in the control of distension-induced peristalsis in the mouse small intestine. J Physiol 506: 843856, 1998.[Abstract/Free Full Text]
- Huizinga JD, Thuneberg L, Vanderwinden JM, and Rumessen JJ. Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders. Trends Pharmacol Sci 18: 393403, 1997.[CrossRef][ISI][Medline]
- Jeffrey B, Udaykumar HS, and Schulze KS. Flow fields generated by peristaltic reflex in isolated guinea pig ileum: impact of contraction depth and shoulders. Am J Physiol Gastrointest Liver Physiol 285: G907G918, 2003.[Abstract/Free Full Text]
- Lammers WJEP. Spatial and temporal coupling between slow waves and pendular contractions. Am J Physiol Gastrointest Liver Physiol 52: G898G903, 2005.[CrossRef]
- Lammers WJ, Dhanasekaran S, Slack JR, and Stephen B. Two-dimensional high-resolution motility mapping in the isolated feline duodenum: methodology and initial results. Neurogastroenterol Motil 13: 309323, 2001.[CrossRef][ISI][Medline]
- Lammers WJ, Stephen B, Arafat K, and Manefield GW. High resolution electrical mapping in the gastrointestinal system: initial results. Neurogastroenterol Motil 8: 207216, 1996.[ISI][Medline]
- Macagno EO, Christensen J, and Lee CL. Modeling the effect of wall movement on absorption in the intestine. Am J Physiol Gastrointest Liver Physiol 243: G541G550, 1982.[Abstract/Free Full Text]
- Mangel AW, Connor JA, and Prosser CL. Effects of alterations in calcium levels on cat small intestinal slow waves. Am J Physiol Cell Physiol 243: C7C13, 1982.[Abstract/Free Full Text]
- Melville J, Macagno E, and Christensen J. Longitudinal contractions in the duodenum: their fluid-mechanical function. Am J Physiol 228: 18871892, 1975.[Abstract/Free Full Text]
- Sarna SK and Otterson MF. Small intestinal physiology and pathophysiology. Gastroenterol Clin North Am 18: 375404, 1989.[ISI][Medline]
- Schulze-Delrieu K. Visual parameters define the phase and the load of contractions in isolated guinea pig ileum. Am J Physiol Gastrointest Liver Physiol 276: G1417G1424, 1999.[Abstract/Free Full Text]
- Shahbazian A, Heinemann A, Schmidhammer H, Beubler E, Holzer-Petsche U, and Holzer P. Involvement of mu- and kappa-, but not delta-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine. Br J Pharmacol 135: 741750, 2002.[CrossRef][ISI][Medline]
- Spencer NJ, Smith CB, and Smith TK. Role of muscle tone in peristalsis in guinea-pig small intestine. J Physiol 530: 295306, 2001.[Abstract/Free Full Text]
- Thuneberg L and Peters S. Toward a concept of stretch-coupling in smooth muscle. I. Anatomy of intestinal segmentation and sleeve contractions. Anat Rec 262: 110124, 2001.[CrossRef][ISI][Medline]
- Trendelenburg P. Physiologische und pharmakologische Versuche Uber die Dunndarmperistaltik. Naunyn Schmiedebergs Arch Pharmacol 81: 55129, 1917.[CrossRef]
- Waterman SA and Costa M. The role of enteric inhibitory motoneurons in peristalsis in the isolated guinea-pig small intestine. J Physiol 477: 459468, 1994.[Abstract]
- Wood JD. Excitation of intestinal muscle by atropine, tetrodotoxin, and xylocaine. Am J Physiol 222: 118125, 1972.[Free Full Text]