Migrating Action Potential Complex Research Articles

Getting a Handle on Cholera and the Circuits Controlling Intestinal Motility

Getting a Handle on Cholera and the Circuits Controlling Intestinal Motility

Effect of Escherichia coli heat-labile enterotoxin on the myoelectric activity of the duodenum in weaned pigs.

The objective of the present study was to elucidate the effect of subclinical doses of Escherichia coli heat-labile enterotoxin (LT) on the antro-duodenal myoelectric activities of weaned pigs. Twelve weaned pigs were surgically implanted with three pairs of electrodes on the antrum 3 cm before the pylorus, 5 and 20 cm after the pylorus on the duodenum, respectively. An infusion cannula was inserted into the duodenum between duodenal electrodes. Using a wireless telemetry recording system, an electromyography (EMG) tracing lasting at least 24 h was recorded as the control, then another 24-h EMG recording was performed with a bolus intraduodenal infusion of LT (0.1 and 0.5 microg/kg b.w.). After a 1- to 2-day break, a 5-fold higher dose of LT was administered using the same protocol. In the antrum, LT administration barely modified the EMG signal. However, in the duodenum it prolonged the duration of phase II and the migrating myoelectric complex (MMC) cycle when compared with the control. The number of duodenal MMC cycles was also significantly diminished. Moreover, the migrating velocity of phase III was increased. The migrating action potential complex (MAPC) was present both without and with LT, but occurred more frequently following LT administration. In conclusion, LT caused a dose-dependent, lagged alteration in the duodenal MMC in weaned pigs, involving a reduction of the MMC number by lengthening phase II, increased phase III migration velocity, and increased MAPC frequency. The disturbances did not, however, result in diarrhoea and may reflect the induction of a local protection mechanism of the gut to expel unwanted foreign content from the lumen of the upper gut.

Effect of cloned Salmonella typhimurium enterotoxin on rabbit intestinal motility

We analysed the small intestine myoelectric responses of anesthetized New Zealand albino rabbits to Escherichia coli lysates containing an enterotoxin cloned from Salmonella typhimurium. Migrating action potential complex, which consisted of rapid bursts of action potentials and secretion of fluid, was observed only in ileal loops injected with the enterotoxin-containing lysate. Migrating action potential complex produced by Stn usually propagated aborally, which was typical of cholera toxin, but orad or bidirectional propagation occurred from a single point of origin when activity was intense. Gell lysates from an E. coli clone containing vectors alone, as well as proximal control segments injected with phosphate-buffered saline, gave neither a change in motility nor fluid secretion. These results show that Stn caused dramatic changes in intestinal motility and substantial fluid production.

Effect of cloned Salmonella typhimurium enterotoxin on rabbit intestinal motility.

We analysed the small intestine myoelectric responses of anesthetized New Zealand albino rabbits to Escherichia coli lysates containing an entertoxin cloned from Salmonella typhimurium. Migrating action potential complex, which consisted of rapid bursts of actions potentials and secretion of fluid, was observed only in ileal loops, injected with the enterotoxin-containing lysate. Migrating action potential complex produced by Stn usually propagated aborally, which was typical of cholera toxin, but orad or bidirectional propagation occurred from a single point of origin when activity was intense. Cell lysates from an E. coli clone containing vectors alone, as well as proximal control segments injected with phosphate-buffered saline, gave neither a change in motility nor fluid secretion. These results show that Stn caused dramatic changes in intestinal motility and substantial fluid production.

Migrating spike complex in the small intestine of the fasting cat.

This study characterizes the migrating spike complex (MSC) in the small intestine of the awake fasting cat and compares the MSC with interdigestive activity in the small intestine of other species. Electrical activity in each of 12 cats with implanted electrodes showed MSCs, bands of spike potentials which attenuated slow-wave frequency and amplitude as the MSCs progressed distally. MSCs occurred at variable frequency with intervals ranging from < 1 min to > 5 h and averaged 51.2 +/- 2.8 (SE) min. MSCs migrated at 1-8 mm/s, accelerating distally; the duration decreased distally such that the length of the bowel in a burst (2-3 cm proximally) was conserved. The MSC was associated with an intense prolonged contraction of duration similar to that of the MSC. Sometimes the MSCs occurred in close association, and when an MSC period was < 5.7 min, the second MSC propagated at a slower rate than the first. Frequently, a brief series of slow wave-associated spikes preceded an MSC. MSCs were not associated with slow waves. The MSC differs in several respects from the migrating myoelectric complex of other laboratory animals and is more appropriately classified in a category that includes giant migrating spikes, prolonged propagated contractions, power contractions, and migrating action potential complexes.

Myoelectric activity of the small intestine in enterotoxin-induced diarrhea of calves

Summary Electrodes were surgically implanted at 15-cm intervals in the jejunum and ileum of 4 healthy neonatal calves so that myoelectric activity could be recorded on 2 consecutive days. On the first day, each calf received a control treatment, and myoelectric activity was recorded for 340 minutes. Phase I was recorded for a mean of 175.8 ± 22.8 minutes (51.5%), phase II for 124 ± 27.4 minutes (36.5%), and phase III for 40.3 ± 6 minutes (11.9%). On the second day, each calf was treated with approximately 200 μg of heat-stable enterotoxin (STa) of Escherichia coli orally. All calves developed diarrhea after the administration of STa. Phase I was recorded for a mean of 92.5 ± 42.3 minutes (27.2%), phase II for 227.3 ± 52.5 minutes (66.9%), and phase III for 20.3 ± 11.4 minutes (6.0%). Increase in phase II and decrease in phases I and III after STa administration were significant (P &lt; 0.05). Duration of the migrating myoelectric complex was longer after STa administration (median, 64 minutes), compared with the control treatment (median, 54 minutes). Minute rhythms, recorded on the day of toxin administration, ranged from 49 to 153 minutes. There was no difference between the number of migrating action potential complexes on the control days (range, 1 to 10), compared with those on treatment days (range, 1 to 14). These findings are suggestive that enterotoxin-induced diarrhea of calves is accompanied by increased total spiking activity and minute rhythms in the distal portion of the jejunum and ileum.

Effects of Vibrio cholerae recombinant strains on rabbit ileum in vivo: Enterotoxin production and myoelectric activity

Previous studies have identified the effects of Vibrio cholerae and its enterotoxin, choleragen (CT A+B+), on the myoelectric activity of rabbit ileal loops in vivo. The response was defined as the migrating action potential complex, the single ring contraction that propels luminal contents aborad. In this study the same rabbit model is used to assess whether migrating action potential complex activity or fluid output is induced by recombinant strains of V. cholerae that produce no subunit of cholera toxin (CT A−B−) or only by the inactive binding subunit (CT A−B+). Three live strains were studied: El Tor wild-type N16961 (CT A+B+) and recombinant strains CVD106 (CT A−B+) and JBK70 (CT A−B−). Controls received sterile culture broth. Migrating action potential complex frequency in animals inoculated with CT A+B+ was significantly increased compared with that in all other experimental groups (P < 0.01). Fluid output was also increased in animals inoculated with CT A+B+ compared with fluid output in all other groups (P < 0.05). Migrating action potential complex frequency and fluid output in rabbits given CT A−B+ or CT A−B− did not differ from activity in controls. How these recombinant strains induce diarrhea is unknown, but the mechanism may involve bacterial colonization or production of an unknown toxin.

Purified choleragenoid does not induce migrating action potential complex activity in rabbit ileum in vivo.

Purified choleragenoid does not induce migrating action potential complex activity in rabbit ileum in vivo.

Myoelectric activity of the ileum, cecum, and right ventral colon in ponies during interdigestive, nonfeeding, and digestive periods

SUMMARY Myoelectric activity of the ileum, cecum, and right ventral colon (rvc) was studied in 4 mature ponies. Eight Ag-AgCl bipolar recording electrodes were sutured to the seromuscular layer of the ileum (2 electrodes), cecum (4 electrodes), and RVC (2 electrodes). Myoelectric activity was studied beginning 10 days after surgery. Eight, 60-minute recording sessions were performed in each pony during the interdigestive period, which was the period 3 to 7 hours after the morning feeding. On separate days, food was withheld for 24 hours, and 90-minute recordings were obtained during the nonfeeding period. Ponies were then fed a normal ration, and recordings were continued to obtain data for the digestive (feeding) period. All phases of the migrating myoelectric complex were seen at both ileal electrodes during the interdigestive period, including the periods of no spiking activity (phase 1), irregular spiking activity (phase 2), and regular spiking activity (phase 3). Phase 2 occupied 77% of the total recording time, and the mean duration of phases 1,2, and 3 was 3.4 ± 0.2, 12.8 ± 1.2, and 6.7 ± 0.7 min, respectively. Frequency of ileal slow waves was 11.8 ± 0.1/min, and spike burst conduction velocity was 4.7 ± 0.3 cm/s. A complete migrating myoelectric complex was seen in 11 of 32 tracings (34%) and had a mean duration of 24.2 ± 2.6 min. The ileal migrating action potential complex, most often seen in phase 2, had a frequency of 4.8 ± 0.5 spike bursts/h and a conduction velocity of 13.6 ± 0.4 cm/s. The migrating action potential complex was detected directly before retrograde cecal myoelectric activity 73% of the time, indicating possible myoelectric coupling of the ileum and cecum. Motility patterns recognized in the cecum included: pattern I, spike bursts beginning at the apex and conducted to the cranial base; pattern II, spike bursts beginning at the caudal base and conducted to the apex; pattern III, spike bursts beginning at the cranial base and conducted to the apex; and pattern IV, termed the progressive pattern, beginning at the cecal apex, conducted through the cecal base and cecocolic orifice and into the RVC. The progressive pattern was detected at a frequency of 34.2 ± 1.8 spike bursts/h and was often preceded by (71%), followed by (64%), or preceded and followed by (51%) pattern I or II. This recurring sequence of cecal myoelectric events was termed the cecal myoelectric complex. In the RVC, 2 patterns of myoelectric activity were seen: aborally directed propulsive spike bursts (3.6 ± 0.6 spike bursts/h) and orally directed retropulsive spike bursts (7.2 ± 1.2 spike bursts/h), confirming that propulsion and retropulsion exist in the RVC. Nonfeeding caused a significant decrease in the frequency of ileal migrating action potential complex (P = 0.008), cecal pattern III (P = 0.003), and the progressive motility pattern (P = 0.003). Nonfeeding caused a significant decrease (P ≤ 0.009) in the appearance of the cecal myoelectric complex. Feeding caused a significant increase (P = 0.003) in the mean frequency of the progressive pattern compared with the nonfeeding period, but this was significantly less than during the interdigestive period (P = 0.003).

Migrating action potential complexes--a feature of normal jejunal myoelectric activity in the rat.

To determine if migrating action potential complexes (MAPCs) are a feature of normal motility, Hooded-Lister rats (100-150 g) were surgically prepared with three pairs of bipolar jejunal electrodes spaced 2.5 cm apart and with a jejunostomy tube for motility recording. Animals were studied conscious and unrestrained on postoperative day 14 after an 18-h fast. Intestinal myoelectric and motor activity was recorded for a 1-h interval in 24 animals that continued to fast and in 12 animals that were allowed to feed for 10 min. Fasting rats had a jejunal slow wave frequency of 32 +/- 2 contractions/min which did not differ significantly after feeding. Migrating myoelectric complexes (MMC) were clearly identified in all fasting animals and had a cycle period of 10.0 +/- 3.6 min. MAPCs were seen during phase II in 83% of MMCs and had an average distribution of 4.2 +/- 3.9/MMC. Feeding abolished the MMC and initiated a continuous irregular pattern of electrical spiking and associated contractile activity. Migrating action potential complexes were seen after feeding with a frequency of 1.8 +/- 0.4/min. It is concluded that MAPCs are a common feature of normal interdigestive phase II and also of postprandial jejunal motility in the rat. This supports the hypothesis that the MAPC is a basic propulsive motor pattern intrinsic to normal intestinal function.

Jejunal myoelectrical activity in the conscious neonatal pig.

The purpose of this study was to define and quantify patterns of normal jejunal myoelectrical activity in the conscious neonatal pig. Twelve 3-day-old piglets were obtained from a local herd. At 7 days of age four bipolar Ag-AgCl electrodes were surgically implanted at 5 cm intervals on the jejunum. Piglets were divided into fed (n = 7) and fasted (n = 5) groups and a minimum of four daily recordings were made from each pig between 7 and 14 days of age. Slow wave and spike activity were seen in all animals. Slow waves occurred at a frequency of 17.0 +/- 0.3 cycles/min (c.p.m.) in fed and 16.8 +/- 0.2 c.p.m. in fasted piglets. Spike activity predominated, occurring in characteristic migrating myoelectrical complexes (m.m.c.s.) and occupying 79% of the recording time in fed and 73% in fasted piglets (P less than 0.05). The activity front (phase 3) of the m.m.c. recurred every 47.7 +/- 2.4 min in fed, and 50.9 +/- 2.3 min in fasted piglets. The m.m.c. periodicity in both groups was irregular, with a range of 4-145 min in fed, and 8-104 min in fasted piglets. Activity fronts lasted 4.8 +/- 0.1 min in fed and 4.4 +/- 0.1 min in fasted piglets. All piglets demonstrated intense, short (2.5-5.0 s), distinct bursts of intense spike activity (migrating action potential complexes, m.a.p.c.s.). These were rapidly conducted in an aboral direction at a velocity of 1.8 cm/s in fed, and 0.8 cm/s in fasted piglets (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Migrating action potential complex: unmasked by 6-hydroxydopamine.

We have previously described the myoelectric characteristics of a single moving ring contraction, the migrating action potential complex (MAPC), in rabbit ileal loops exposed to certain bacteria or their enterotoxins. The MAPC is thought to act as a defense mechanism of the host, clearing unwanted substances from the lumen. In the present study, 6-hydroxydopamine, a substance that selectively destroys adrenergic varicosities containing the neurotransmitter norepinephrine, unmasked the MAPC from the activity front of the migrating motor complex in an unanesthetized rat model. The animals developed diarrhea and lost weight. The study suggests that the MAPC may also be a physiological complex and under the modulation of the enteric nervous system. The MAPC may not be seen under normal control conditions because the complex migrates with the activity front and is under inhibitory control. Destroying the inhibitory mechanisms unmasked the MAPC from the activity front of the migrating motor complex and allowed neural transmission of the ring contraction.

Motility of the small intestine: a look ahead.

Motility of the gastrointestinal tract has become an important discipline of gastroenterology. In this paper we review important observations made during the early development of this discipline, note the current level of knowledge, and look ahead to some of the questions we believe will be addressed in the near future. Is the slow wave the action potential equivalent of the longitudinal muscle layer? How does the migrating action potential complex interrelate with the migrating myoelectric complex--are they two separate complexes under different control mechanisms? How do the myenteric plexus neurons relate to these complexes? Does the muscularis mucosa control the contraction and relaxation of the villous tips? Is there a finite area in the small intestine that can function as the pacemaker? How important are substances within the lumen in controlling motility? Finally, we emphasize the importance of structure and function of the plexus neurons in motility studies. We also stress the importance of collaboration and a multidisciplinary approach for future understanding of the mechanisms of the small intestine in health and disease.

Alterations in motor function of the small intestine from intravenous and intraluminal cholecystokinin

Cholecystokinin has been found within the lumen of the gastrointestinal tract; however, its effect on intestinal motility has not been studied. We examined the effect of intraluminal and intravenous infusion of the octapeptide of cholecystokinin (CCK-OP) on myoelectric activity in the intestine of rabbits. CCK-OP was infused intraluminally at 1,000 ng X kg-1 X h-1, and portal venous blood samples were obtained hourly for plasma immunoreactive CCK. CCK-OP was also infused intravenously at a similar rate, and hourly peripheral venous blood samples were obtained for plasma immunoreactive CCK. Myoelectric activity was monitored in a 12-cm ligated ileal segment and the proximal adjacent small intestine after the infusion of intraluminal or intravenous CCK-OP. Intraluminal infusion of CCK-OP caused a significant increase (P less than 0.01) in both migrating action potential complexes (MAPC) and repetitive bursts of action potentials (RBAP) (3.1 +/- 0.8 MAPC/h and 4.6 +/- 1.3 RBAP/h). In contrast, intravenous CCK-OP induced only repetitive bursts of action potentials (8.3 +/- 1.7 RBAP/h, P less than 0.01). In summary, alterations in intestinal motility may vary according to the route of administration of the individual peptide. Furthermore, results from these studies suggest that intraluminal release of regulatory peptides may be important in the modulation of intestinal motility.

Influence of coronavirus (transmissible gastroenteritis) infection on jejunal myoelectrical activity of the neonatal pig

Four silver—silver chloride electrodes were surgically implanted at 5-cm intervals on the jejunal serosa of 7 neonatal pigs. Daily recordings, 7 h in duration, were made from each piglet beginning 3 days after surgery. Characteristic migrating motility complexes and short, distinct (2.5–5.0 s), rapidly aboral migrating bursts of intense spike activity (“migrating action potential complexes”) were seen in all preinfection recordings. Piglets were inoculated with a 1-ml oral dose of a 0.1% gut suspension from coronavirus (transmissible gastroenteritis) infected pigs. This resulted in inappetence, vomiting, and diarrhea, most marked on the second day postinfection, but which had abated by the third day. When compared to recordings from both fed and fasted noninfected (control) animals, infection significantly altered jejunal myoelectrical activity by (a) shortening the duration of the migrating motility complex on day 1 postinfection and prolonging it on day 2, (b) increasing the number of abnormal activity fronts, and (c) decreasing the number of migrating action potential complexes. Slow wave frequency and the duration of phase 3 of the migrating motility complex were unaffected. When compared to fed control animals, infected piglets also showed a slight shortening of phase 1 of the migrating motility complex on day 1 postinfection and a prolongation on days 2 and 3, as well as a shortening of phase 2 on the second and third days postinfection. Changes in myoelectrical activity were not solely due to decreases in food intake, as abnormalities persisted when food intake returned to normal on postinfection day 3, and disruption of the activity front and migrating motility complex duration were purely transmissible-gastroenteritis-virus-induced phenomena. These findings suggest that infection with transmissible gastroenteritis virus disrupts organized propulsive activity in the jejunum of the neonatal pig.

Altered motility and duration of bacterial overgrowth in experimental blind loop syndrome.

To better understand the pathogenesis of the increased motility previously described in the blind loop rat, we studied the relationship between duration of bacterial overgrowth and both myoelectric activity and bacterial flora in this model. Myoelectric studies and quantitative bacterial cultures were performed on self-filling and self-emptying (control) blind loop rats one, two, and three weeks postoperatively. All self-filling blind loop rats had greater random action potential activity and higher frequencies of migrating action potential complexes than controls (P less than 0.05). One-week self-filling blind loop rats had a higher frequency of migrating action potential complexes (P less than 0.05) and a higher ratio of counts of Escherichia coli to Bacteroides species (P less than 0.05) than the two- or three-week self-filling blind loop groups. Thus, qualitative changes in myoelectric activity occur during the development of bacterial overgrowth in the blind loop rat which may reflect evolving alterations in the bacterial flora.

Trichinella spiralis: Intestinal myoelectric activity during enteric infection in the rat

The objective was to characterize changes in the host's small intestinal smooth muscle contractile activity caused by the enteric stages of the nematode, Trichinella spiralis, during primary infection. Myoelectric activity was recorded from electrodes permanently implanted on the seromuscular surface of the small bowel in conscious, unrestrained rats during the first 2 weeks postinfection (PI). Several myoelectric parameters examined collectively indicated that smooth muscle function of the small bowel was altered by infection. A decrease in contractile activity was indicated by reductions in electrical slow wave and spike potential frequencies that were maximal 6–12 days postinfection. Normal coordinated contractile behavior was also impaired, as evident from a reduction in the frequency of migrating myoelectric complexes. An infection-induced qualitative change occurred designated as a migrating action potential complex. This unusual spiking activity swept down the bowl rapidly, occurred with greatest frequency 2–6 days PI, and coincided with the disruption of the normal migrating myoelectric complex. It is concluded that recordings of intestinal myoelectric activity provide sensitive, quantifiable correlates of contractile patterns throughout the intestinal phase of trichinellosis in a single host.

Purified Shigella enterotoxin does not alter intestinal motility.

A purified Shigella enterotoxin (pST) and a cell-free lysate with pST removed (CFL-pST) from the whole-cell lysate of Shigella dysenteriae 60 R were used to study their effect on the myoelectric activity and mucosal integrity of rabbit ileal segments. We have previously defined two myoelectric patterns: the migrating action potential complex and repetitive bursts of action potentials that occur in response to certain bacteria and their enterotoxins. The in vivo model consisted of isolated ileal segments in male New Zealand White rabbits. The segments were infused with sterile saline (1 ml/h), pST (2.4-micrograms injection), or CFL-pST (1 ml/h). Myoelectric activity in the segments exposed to pST was similar to that with the saline infusion, but CFL-pST induced significant alterations in myoelectric activity in the form of repetitive bursts of action potentials. The mucosa of the segments exposed to pST showed only mild inflammatory changes. In contrast, CFL-pST caused moderate to severe inflammatory changes with enterocyte necrosis. These studies show that pST, a known enterotoxin, did not alter myoelectric activity and had no significant effect on the integrity of ileal mucosa, as determined by light microscopy. CFL-pST caused both inflammation and tissue necrosis with significant alterations in motor activity. These studies suggest that S. dysenteriae 60 R produces a substance or substances other than pST that cause florid in vivo cytotoxicity and alter myoelectric activity.

Altered myoelectric activity in the experimental blind loop syndrome.

Nutrient malabsorption and diarrhea are characteristic of the blind loop syndrome. Alterations in motility have been implicated as a cause of bacterial overgrowth, but the possibility that altered motility may result from alterations in the flora has not been explored. The purpose of this study was to characterize the myoelectric activity of the small intestine in the blind loop rat model. Eight groups of rats were studied: rats with self-filling blind loops, which develop bacterial overgrowth; rats with self-emptying blind loops, which are surgical controls that do not develop overgrowth; unoperated litter mates; rats with self-filling blind loops and unoperated controls treated with chloramphenicol, 200 mg/d i.p.; rats with surgically removed self-filling blind loops; operated control rats; and gnotobiotic rats with self-filling blind loops. In the untreated rats with self-filling blind loops, there was altered myoelectric activity characterized by an increased percentage of slow waves occupied by action potentials and by organized activity similar to the migrating action potential complex. Migrating action potential complex activity and percentage of slow waves occupied by action potentials were significantly decreased with chloramphenicol therapy; that decrease correlated with a decrease in aerobes and anaerobes. Migrating action potential complex activity was abolished in rats with surgically removed self-filling blind loops; they also showed a significant decrease in percentage of slow waves occupied by action potentials. Gnotobiotic rats with self-filling blind loops showed no alteration in myoelectric activity. These data indicate: (a) bacterial overgrowth is associated with a significant increase in percentage of slow waves occupied by action potentials and migrating action potential complex activity; (b) chloramphenicol significantly reduced both percentage of slow waves occupied by action potentials and migrating action potential complex activity; and (c) surgical removal of the loop reduced the alterations in motor function. This study suggests that the altered myoelectric activity in this model of bacterial overgrowth was due, in part, to the abnormal bacterial flora and supports the concept that alterations in motility may contribute to the diarrhea that is characteristic of the blind loop syndrome.

Migrating action-potential complexes in vitro in cholera-exposed rabbit ileum.

The objective of this study was to determine whether cholera-exposed rabbit ileum exhibits altered myoelectric activity in vitro, without central nervous system connections. Whole-cell lysate of Vibrio cholerae, 100 mg in 1 ml saline, was injected into the jejunum of New Zealand White rabbits. Segments of ileum were removed at 12 and 24 h after inoculation and studied in vitro using myoelectric recording techniques. Propagating ring contractions were visualized and corresponded to intense action-potential activity that propagated over consecutive electrode sites. This altered myoelectric activity was similar to the previously described migrating action-potential complex (MAPC) in vivo after infection of rabbit ileum with live V. cholerae, its wholecell lysate, or the purified enterotoxin choleragen, with one exception. All MAPC activity propagated aborally in the in vivo-infected loops; in contrast 26% of the MAPCs propagated retrograde in the in vitro loops. Control segments were injected with saline, and no in vitro MAPCs were observed. Thus, the MAPC stimulated by cholera toxin may be maintained by the enteric nervous system of the gut wall. Although a role for extrinsic nerves is not excluded, our observations suggest that the small intestine may work autonomously, independent of the central nervous system.