Regulation of the fasting enterohepatic circulation of bile acids by the migrating myoelectric complex in dogs.

UNLABELLED: The purpose of this study was to correlate the fasting enterohepatic circulation (EHC) of bile acids with the migrating myoelectric complex. Four dogs were surgically provided with a functional cholecystectomy, a duodenal cannula for direct vision cannulation of the common bile duct, and 12 bipolar electrodes implanted from stomach to terminal ileum. Bile was collected in equal-volume, timed aliquots over 6 to 10 h. Aliquots were sampled and either returned to the duodenum for study of the intact EHC, or collected and retained in order to study the time course of the bile acid pool washout. In the washout experiments boluses of radiolabeled taurocholic acid were instilled into the duodenum before and after duodenal phase III of the migrating motor or myoelectric complex (MMC). In another group of experiments the bile acid pool was washed out and during a continuous duodenal infusion of taurocholic acid bile was collected to study the pattern of hepatic secretion. RESULTS: (a) In all experiments, a single broad peak of bile flow and bile acid secretion occurred at 35-55% of the MMC migration time. At this time the MMC had migrated to a point 70-85% of the distance along the small intestine. (b) During bile acid pool washout the peak of bile flow and bile acid secretion occurred with the distal migration of the first MMC and then bile flow and bile acid secretion rates decreased to a minimum and stabilized. (c) In bile acid pool washout experiments the radiolabeled bile acids instilled into the duodenum prior to duodenal phase III were secreted and peaked with peak endogenous bile acid secretion. The secretion of radiolabeled bile acids instilled into the duodenum after duodenal phase III was delayed until the subsequent cycle of the MMC. 88% of the bile acid pool collected over 6 h was secreted during the distal migration of the first MMC (2.4 +/- 0.4 h). (d) After bile acid pool washout and during continuous duodenal infusion of taurocholic acid, hepatic bile flow and bile acid secretion continued to fluctuate with the same pattern observed with the EHC intact. CONCLUSIONS: (a) In the fasting state, the transport of intestinal bile acids to the liver is pulsatile rather than continuous and is determined by the MMC. Maximum hepatic secretion occurs when phase III of the MMC propels the intraluminal bile acid pool to its site of absorption in the distal small bowel. (b) The "housekeeping" action of the MMC is very efficient and clears 88% of the 6-h washout bile acid pool in one pass.

Multielectrode mapping of slow-wave activity in the isolated rabbit duodenum.

The technique of multiple simultaneous recordings from a large number of extracellular electrodes (> 100) is currently used in the study of normal and abnormal electrical conduction in the heart and the genesis of cardiac arrhythmias. To investigate whether such a system could also be applied in gastrointestinal electrophysiology, several studies were performed with this technique on segments of isolated rabbit duodenum. A multiple-electrode assembly consisting of 240 silver wires was positioned on the serosal surface of the duodenum, and the recorded signals were, after suitable processing, stored. Thereafter, analysis of all simultaneously recorded slow waves during a selected period of time was performed to reconstruct the pattern of conduction in the duodenum. The first results show that there is a considerable variation in conduction pattern, which is determined by the site of the natural pacemaker. Several experiments were performed to rule out possible deleterious effects of positioning the multiple-electrode assembly on the duodenum. Furthermore, prolonged periods of recording did not influence propagation speed and pattern provided that the positioning of the multiple electrode assembly was performed with care. Entrainment of the natural pacemaker was possible by applying electrical stimuli through 2 of the 240 extracellular electrodes during simultaneous recordings. In conclusion, multisite extracellular mapping of gastrointestinal smooth muscle is possible and can be used to study origin and spread of slow-wave activity.

Disturbances in the propagation of the slow wave during acute local ischaemia in the feline small intestine.

OBJECTIVE AND DESIGN: The normal aborad propagation of the slow wave in the small intestine is easily distorted by pacing, hypoxia or transection. We studied whether acute local ischaemia would also induce serious conduction disturbances and ectopic pacemaking. METHODS: After general anaesthesia and a mid-abdominal incision, a multi-electrode array of 240 extracellular electrodes was positioned on the serosal surface of an exteriorized intestinal loop. Simultaneous recordings of all 240 surface electrodes was performed during a control period and for 5-10 min following local acute arterial occlusion. After the experiments activation maps were constructed describing the pattern of propagation of the slow waves. RESULTS: During control periods, the activation maps showed homogeneous aborad conduction of the slow wave. During acute ischaemia, local areas of inexcitability developed rapidly, merging together to form lines of conduction block. This in turn often provoked the appearance of subsidiary ectopic pacemakers. The location of the conduction blocks as well as that of ectopic pacemakers was highly variable and could disappear and reappear at other sites. CONCLUSION: Within minutes, acute ischaemia disturbed the organized homogeneous aborad propagation of the slow wave leading to pronounced inhomogeneous depression of conduction, local inexcitability, conduction block and the appearance of subsidiary pacemakers.

Wave mapping: detection of co-existing multiple wavefronts in high-resolution electrical mapping.

High-resolution mapping makes it possible to reconstruct and display the conduction pattern of the action potential as it propagates through cardiac or smooth muscles. During slow and regular activity, time mapping of the spread of activation muscles. During slow and regular activity, time mapping of the spread of activation is relatively simple and straightforward. However, when frequencies are high or conduction is slow, such as seen during atrial fibrillation or found in the pregnant uterus, the tracking of individual waves may become more difficult and uncertain. In order to reconstruct the pathway of a single wave, a search and sorting routine was developed which makes it possible to distinguish, track and display individual wavelets. The algorithm is able to detect variations in conduction block, spontaneous shifts in the location of the pacemaker and changes in the direction of conduction. It is less sensitive when two or more wavefronts intermingle in space and time, such as during collision or fusion. Wave mapping is especially useful, in addition to current time mapping, in sorting quickly through the large amount of data produced by high-resolution mapping of electrical activities in cardiac and smooth muscle.

Electrical activities of the muscle layers of the canine colon.

The spontaneous electrical and mechanical activities of the circular and longitudinal muscle layers of the canine colon were studied. The smooth muscle cells of the circular muscle layer exhibited regular, omni-present myogenic slow-wave activity at a frequency ranging from 4 to 7 c/min. With intracellular micro-electrodes, the slow-wave amplitude was 21-38 mV and its duration 3-6 sec. The 'resting' membrane potential was -60 to -76 mV. Some slow waves had superimposed spike bursts on their peak depolarizations and only these were associated with phasic contractions. It is concluded that they serve a pace-maker function similar to their counterpart in the small intestine. The longitudinal muscle layer exhibited periods of electrical activity alternating with periods of electrical quiescence. During the activity periods electrical oscillations occurred at a frequency of 13-35 c/min with spikes on top of them. Each electrical activity period was associated with a prolonged 'tonic' contraction. The duration of these periods was 30-120 sec and their frequency 0.4-1.1 period/min. This activity is similar to that recorded from the longitudinal muscle of the guinea-pig caecum despite the anatomical differences. The electrical activity periods of the longitudinal muscle appeared to require an excitatory input (stretch and/or acetylcholine release). Provided the strips were not excessively stretched, atropine abolished all electrical and motor activity. Stretching prolonged the electrical activity periods until they eventually fused together and the muscle developed maintained tone. Simultaneously recording from both layers showed that, although electrotonic spread between the two layers is probably insignificant, the activity of the two layers was co-ordinated. Only those slow waves of the circular layer that occurred during the electrical activity periods of the longitudinal layer had superimposed spikes. It is suggested that this co-ordination may indicate that the two muscle layers may be commanded by a common input from periodically active, cholinergic intramural neurones. It is proposed that the complex patterns of colonic electrical and motor activities may be explained as consisting of two major components: one arising from the longitudinal (long spike bursts, high-frequency oscillations and tonic contractions) and the other from the circular layer (slow waves, short spike and phasic contractions). Simultaneous electrical records from the two muscle layers and the mucosa failed to show a consistent relationship between the mucosal record and the activity of either layer. Caution should be exercised in the interpretation of intraluminally derived electrical recordings.

Modulation of canine antral circular smooth muscle by acetylcholine, noradrenaline and pentagastrin.

1. The effects of acetylcholine, noradrenaline and pentagastrin on the action potential of canine antral circular muscle were determined using the intracellular micro-electrode technique. 2. Acetylcholine increased the amplitude and duration of the plateau potential of the action potential. Since these effects were blocked by atropine but not by hexamethonium, the effects of acetylcholine were on muscarinic receptors, probably located on the smooth muscle cell. 3. Pentagastrin 2 x 10(-10) M increased the size of the plateau potential and the frequency of the action potential; pentagastrin 1 x 10(-9) M increased the frequency of the action potential complex and produced a marked diastolic depolarization between action potentials. The effect on the size of the plateau potential was biphasic. The amplitude and half-time duration of the plateau potential increased in the first 3 min, but thereafter, during steady-state conditions, they were the same as or slightly greater than those obtained in Krebs solution. 4. All the effects produced by pentagastrin were due to a direct action on the smooth muscle cell. 5. Noradrenaline decreased the size of the plateau potential but increased its frequency; high concentrations (greater than 10(-5) M) additionally produced a diastolic depolarization between action potentials. These effects were mediated primarily by alpha-adrenoceptors presumably located on the smooth muscle cell. 6. It was concluded that the substances studied primarily alter the size of the plateau potential in antral circular muscle. Since phasic contractions are associated with the plateau potential, it is suggested that agents which increase the size of the plateau potential increase the force of the contraction whereas agents which decrease the size of the plateau potential have the opposite effect.

Comparison of the inhibitory effects of cromakalim and pinacidil (potassium channel openers) with those of oxybutynin on stimulated guinea pig and rabbit detrusor muscle strips.

To compare the inhibitory effects of a new group of smooth muscle relaxants, the potassium channel openers cromakalim and pinacidil, with those of oxybutynin on detrusor muscle stimulation in animals. Detrusor strips of guinea pigs (n=16) and rabbits (n=20) were mounted in organ bath for recording of isometric tension. Alpha,beta-methylene ATP (10(-7), 10(-6), 10(-5) M), carbachol (10(-6), 10(-5), 3 x 10(-5), 5 x 10(-5) M) and transmural electrical-field stimulation (TES) were applied and concentration-response curves in the absence or presence of cromakalim (10(-6), 10(-5) M), pinacidil (10(-5), 5 x 10(-5) M) and oxybutynin (10(-5), 5 x 10(-5) M) were generated. All curves were displaced to the right in a concentration-dependent manner. The order of potency of inhibition was as follows: alpha,beta-methylene ATP (pinacidil>oxybutynin>cromakalim in guinea pigs; pinacidil>cromakalim>oxybutynin in rabbits); TES (pinacidil>cromakalim>oxybutynin in guinea pigs; cromakalim>oxybutynin>pinacidil in rabbits); carbachol (oxybutynin>pinacidil>cromakalim in guinea pigs; oxybutynin>cromakalim>pinacidil in rabbits). Cromakalim and pinacidil mainly inhibited purinergic-induced (alpha,beta-methylene ATP and TES) detrusor contractions.

Electrical activity of small intestinal smooth muscle and its temperature dependence.

Some important features of the intracellularly recorded electrical control activity of rabbit jejunal smooth muscle and its temperature dependence are reported in this study. This activity consisted of repetitive 18-mV depolarizations (control potentials (CP) or slow waves), which at 37degreesC lasted 2 s and had a frequency of 18/min and arose from a membrane potential of --55 mV. In some cells periods between CP's exhibited "diastolic" progressive depolarizations (intercontrol-potential depolarization), which may be the trigger of the CP in driving cells. While CP was usually monophasic, some cells persistently exhibited a notch early in the plateau phase. We suggest that CP consists of two components, an "initial depolarization" and a "secondary depolarization," which are usually fused together to give a monophasic potential. Cooling reduced CP frequency and prolonged its duration and caused more cells to show notching. While amplitude and rate of CP initial depolarization had low Q10's, duration and rates of onset and offset of the secondary depolarization had higher Q10's. Thus, the process responsible for secondary depolarization is more sensitive to temperature thant that underlying initial depolarization of the CP.

Electrogenic sodium pumping in rabbit small intestinal smooth muscle.

Oscillations in the activity of an electrogenic Na pump has been suggested as the ionic mechanism underlying the intestinal control potential (slow wave). We investigated the electrogenicity of this pump in rabbit jejunal smooth muscle. Potassium admission to Na-rich tissues caused a large increase in membrane potential which after 10--20 min decreased toward values comparable with those of normal tissues. This hyperpolarization far exceeded EK and could be prevented by cooling or by ouabain. No hyperpolarization occurred upon K admission to Li-rich tissues in the absence of Na. Thus, the pump in this tissue can operate electrogenically. Goldman's equation was modified so as to account for the pump's contribution to the membrane potential. Using this equation, the calculated contribution of the pump, under normal "steady-state" conditions, is unlikely to exceed a few millivolts. It is concluded that although the pump in this tissue can be electrogenic, its contribution may be smaller than that required if the intestinal control potential resulted from rhythmic turning off and on of the electrogenic Na pump.

Neural control of the intestinal migrating myoelectric complex. A pharmacological analysis.

A pharmacological analysis of the participation of autonomic nerves in the control of the intestinal migrating myoelectric complex (MMC) was conducted on six conscious fasting dogs with implanted bipolar electrodes. All dogs exhibited regularly recurring MMC's. Hexamethonium (2-10 mg/kg i.v.) or atropine (25-100 micrograms/kg i.v.) immediately suppressed all spiking activity, stopped the progression of the ongoing complexes, and prevented the initiation of new complexes for 2.5 to 5 h. Phentolamine (2-4 mg/kg i.v.) and propranolol (2 mg/kg i.v.) given separately or in combination had no observable effect on any of the different phases of the complex, its progression, or its frequency. Phenylephrine (0.5-1 mg/kg) inhibited the spiking phases of the complex. Isopropylnoradrenaline had no effect on the complex at doses (up to 30 micrograms/kg) which produced maximal cardiac chronotropic effect. The effects of these agonists were totally blocked by the doses of respective adrenergic antagonists used. Phenoxybenzamine given in a dose of 10-15 mg/kg i.v. produced effects similar to atropine apparently owing to blockade of cholinergic muscarinic receptors. It is concluded that (a) the regular spiking phases of the migrating complex result from cyclical and sequential activation of preganglionic fibers forming nicotinic synapses on postganglionic cholinergic excitatory neurones; and (b) the function of adrenergic nerves is not normally required for the MMC.

Intracellular electrical activity of canine and human gastric smooth muscle.

1. Intracellular recordings were obtained from circular smooth muscle fibres of the canine fundus, corpus, antrum and pylorus as well as from the human corpus and antrum. 2. In the canine stomach, all regions of the stomach except the fundus exhibited spontaneous action potentials. 3. The spontaneous action potential consisted of an upstroke potential and a plateau potential. 4. There were regional differences in the configuration of the plateau potential. Corporal and antral smooth muscle did not normally spike during the plateau potential whereas terminal antral and pyloric muscle usually showed spikes on top of the plateau potential. Near the intermediate sphincter, there was a zone of transition in which oscillations in potential of variable amplitude were superimposed on the plateau potential. 5. The configuration of the action potential of the human stomach was similar to the configuration of the canine action potential when the same region of the stomach was compared. 6. The ionic dependence of the plateau potential was studied in canine stomach in an area where neither oscillations nor spikes occurred. 7. In calcium-free solution, all spontaneous activity stopped. D600 selectively suppressed the size of the plateau potential. 8. Sodium-deficient solution reduced the size of the plateau potential. 9. These results suggest that both calcium and sodium may be involved as current carriers in the generation of the plateau potential.

Vascular effects of some opioid receptor agonists.

Opioid peptides have been implicated in shock-associated hypotension. Our aim was to find out whether opioid agonists have direct vasodilator actions on vascular smooth muscle. The study was conducted on rat abdominal aortic rings. In rings precontracted with either norepinephrine, prostaglandin F2 alpha, or high potassium Krebs (HPK), the effects of the opioid agonists tested (morphine, U50488H, ethylketocyclazocine (EKC), and bremazocine) depended on the precontracting agent used. HPK-precontracted rings were relaxed by all agonists tested. In norepinephrine-precontracted rings, all caused contraction at low concentrations and relaxation at high concentrations except bremazocine, which caused only relaxation. In prostaglandin F2 alpha-precontracted rings, U50488H produced contraction at low concentrations and relaxation at high concentrations while EKC caused only relaxation and morphine or bremazocine caused only contraction. All relaxant responses were endothelium-independent and were antagonized by verapamil but not by a number of antagonists including naloxone. MR2266, propranolol, diphenhydramine, cimetidine, and indomethacin. They may reflect calcium channel blockade. Morphine-induced vasoconstriction was antagonized by high concentrations of of naloxone or mepyramine and may be due to release of histamine by a naloxone-sensitive mechanism. We conclude that (a) the opioid agonists tested exert direct actions on vascular smooth muscle; (b) the nature of the response depended not only on the agonist used and its concentration but also on the agent used to precontract the tissue; and (c) it is unlikely that direct actions of endogenous opioids contribute to the shock-associated hypotension because high doses were needed to elicit them.

The Ehlers-Danlos syndrome and colonic perforation. Report of a case and physiologic assessment of underlying motility disorder.

The Ehlers-Danlos syndrome is a genetically determined disorder of connective tissue which is generally known for its features of fragile, hyperextensible skin, hypermobile joints, and tissue fragility. Less commonly, colorectal complications can occur, including bleeding, prolapse, and diverticulitis. A rare case of colonic perforation associated with Ehlers-Danlos syndrome is presented. Additionally, in vitro electromyographic studies of the colonic tissue were performed which suggested a possible link between abnormal myogenic activity and the colonic perforations. The authors recommend that treatment be either a permanent colostomy or a subtotal colectomy with anastomosis to the rectum for similar cases.

Oesophageal peristalsis in the cat: the role of central innervation assessed by transient vagal blockade.

Studies were performed on five cats to assess the role of extrinsic vagal innervation in the control of peristalsis in the smooth muscle oesophagus. Transient vagal nerve blockade was accomplished by cooling the cervical vagosympathetic nerve trunks previously isolated in skin loops on each side of the neck. Peristalsis throughout the body of the oesophagus was monitored using a continuously perfused multilumen manometry tube. Striated and smooth muscle portions of the esophagus were delineated by abolishing smooth muscle activity with atropine. Secondary peristalsis was assessed by intra-oesophageal balloon distension studies. The threshold volume for balloon-induced secondary peristalsis was lower in the smooth muscle oesophagus. Unilateral vagal blockade reduced the incidence of primary and secondary peristalsis in the striated muscle oesophagus but not in the smooth muscle oesophagus. Bilateral vagal nerve blockade abolished primary swallow-induced peristalsis and secondary peristalsis in both the smooth and striated muscle cat oesophagus. Administration of cholinergic agents or adrenergic blocking agents failed to restore secondary peristalsis in the smooth muscle oesophagus during vagal cooling. We conclude that connections to the central nervous system via the vagal nerve trunks are required for normal secondary as well as primary peristalsis in both the smooth and striated muscle portions of the cat oesophagus.

Spatial and temporal variations in local spike propagation in the myometrium of the 17-day pregnant rat.

Detailed spatial analysis of propagation of individual action potential was performed during spontaneous bursts of activity in the isolated 17-day pregnant rat myometrium. Use was made of high-resolution mapping with simultaneous recordings from 240 extracellular electrodes. Positioning of the electrode assembly by itself did not have any adverse effects, and no differences were found in the period or duration of spontaneous bursts recorded with and without the electrode assembly touching the tissue. The spread of propagation of individual action potentials was reconstructed at several moments during myometrial spike bursts. Both the direction and the sequence of activation of the myometrium were found to be highly variable and depended on 1) the level and spatial dispersion of excitability and 2) whether conduction occurred predominantly in the longitudinal or the circumferential direction. Furthermore, conduction was frequently complicated by the spontaneous occurrence of 1) lines of conduction block, 2) focal sites of pacemaking, or 3) merging of two or more wavelets into a single wave. In contrast, when the myometrium was divided into small segments, activity became much more regular, and both the location of the pacemaker and the direction of propagation were much more stable than in the whole myometrium. In conclusion, spontaneous spatial variations in local spike propagation at the preterm stage could provide for the necessary asynchrony in activation and play a role in the prevention of forceful contractions and premature labor.

Vagal control of canine postprandial upper gastrointestinal motility.

The role of the vagus nerves in the control of postprandial motility in the upper gastrointestinal tract was investigated in four dogs by use of a bilateral cervical cooling blockade technique. On administration of food, the fasting migrating motor complex (MMC) was replaced by the postprandial (feeding) pattern. Feeding pattern duration varied in a dose-dependent manner with either total volume or calories of food. During the feeding pattern, oscillations in lower esophageal sphincter (LES) pressure occurred at time intervals equivalent to the MMC cycle period. Twenty-one control feeding experiments and 17 postprandial vagal blockade experiments were performed, with a minimum of three of each type in each dog. Vagal blockade, initiated at times ranging from 15 min to 4 h after feeding and maintained for up to 5 h, abolished the postprandial activity in the upper gastrointestinal tract. During postprandial vagal blockade, LES pressure was abolished and bursts of contractions were observed only in the upper small bowel, a pattern resembling that observed during vagal blockade in the fasted state. These bursts occurred at the expected times relative to, and their cycle period was not significantly different from, that of the MMCs recorded prior to feeding. Vagal blockade started prior to feeding prevented initiation of the fed pattern, which appeared immediately on termination of the blockade. We conclude that initiation and maintenance of the postprandial pattern in the upper gastrointestinal tract with concurrent inhibition of the fasting MMC normally require vagal integrity. The "clock" controlling the MMC cycle period is not reset by feeding, but its effect on motility is suppressed.

Hemodynamic and catecholamine responses to laryngoscopy with vs. without endotracheal intubation.

To study the relationship between the intensity of the stimulus exerted against the base of the tongue during direct laryngoscopy and the magnitude of associated hemodynamic and catecholamine responses, a study was conducted in 40 ASA I or II patients. Laryngoscopy lasting 40 s was performed with a size 3 Macintosh blade connected to a force-displacement transducer. The intensity of the stimulus exerted during laryngoscopy is expressed by the product of its average force (N) and duration (s) and given as impulse in Ns. Highly significant relationships were found between the impulse during laryngoscopy and the maximal hemodynamic and catecholamine responses. Also, when laryngoscopy was followed by orotracheal intubation, significant relationships were found with steeper slopes of the regression lines for systolic blood pressure, heart rate and plasma epinephrine concentrations. A more rapid regression of hemodynamic data was seen in intubated patients, whereas their plasma catecholamine concentrations regressed more slowly. The mechanisms of the responses to laryngoscopy and orotracheal intubation are proposed to be by somato-visceral reflexes. Stimulation of proprioceptors at the base of the tongue during laryngoscopy induces impulse-dependent increases of systemic blood pressure, heart rate and plasma catecholamine concentrations. Subsequent orotracheal intubation recruits additional receptors that elicit augmented hemodynamic and epinephrine responses as well as some vagal inhibition of the heart.

Lower esophageal sphincter function in the cat: role of central innervation assessed by transient vagal blockade.

Studies were performed on four cats to assess the role of extrinsic vagal innervation in the control of lower esophageal sphincter (LES) function. Both cervical vagal nerves were blocked transiently by cooling. LES pressure was measured using a multilumen manometry tube. LES relaxation was assessed during intraesophageal balloon distension in both the striated and smooth muscle portions of the esophagus. Bilateral vagal nerve blockade lowered the mean LES pressure from 58 +/- 17 to 29 +/- 9 mmHg (P less than 0.01). During vagal blockade, balloon distension in the striated muscle esophagus further reduced sphincter pressure to 16 +/- 4 mmHg (P less than 0.01) and that in the smooth muscle esophagus to 15 +/- 3 mmHg (P less than 0.01). Swallow-induced LES relaxation was abolished during bilateral vagal nerve blockade. During vagal blockade, atropine reduced LES pressure to 10 +/- 1 mmHg, phentolamine to 13 +/- 6 mmHg, and hexamethonium to 10 +/- 4 mmHg (all P less than 0.01). We conclude that 1) normal LES tone in the cat is mediated primarily by two separate neural mechanisms: a vagal cholinergic mechanism and a nonvagal mechanism that utilizes both alpha-adrenergic and cholinergic receptors; 2) local, intramural mechanisms of high threshold are present in the striated and smooth muscle cat esophagus to allow distension-induced reflex inhibition of the LES; and 3) swallow-induced LES relaxation is dependent on vagally mediated central nervous system connections.

Electrical basis of contractions in the muscle layers of the pig colon.

Simultaneous in vitro measurements of electrical and mechanical activities were performed, using suction electrodes and force transducers, respectively, on longitudinal and circular muscle layers of the pig proximal colon. In addition, circular muscle strips were studied with the sucrose gap technique. Spontaneous activity was present in both preparations. In the circular muscle, slow waves with superimposed spikes occurred at a variable frequency, accompanied by phasic contractions. Longitudinal muscle preparations showed a different behavior. Regular appearance of distinct slow waves as described for the circular muscle did not occur. Instead, periods of membrane potential oscillations at a frequency of 41 cycles/min and a duration of approximately 12 s were observed in this layer. Most oscillations had superimposed spikes, and each period of oscillations was associated with a contraction. Spontaneous activity in the circular layer was myogenic in nature but susceptible to innervation and stretch. In contrast, an excitatory stimulus (acetylcholine or stretch) was a prerequisite for activity in the longitudinal layer. Cholinomimetics increased and adrenergic agents decreased the frequency of the slow waves and spiking activity and frequency and force of contractions in the circular muscle. Cholinergic agents increased the activity in the longitudinal muscle into continuous electrical oscillations with spiking activity and concomitant tonic contractile activity, whereas adrenergic agents abolished electrical and mechanical activity. Spontaneous release of acetylcholine occurred, partly due to regenerative activity of myenteric cholinergic nerves. In addition, tonic activity in the noncholinergic nonadrenergic inhibitory neurons decreased circular muscle tone.