Antral Slow Waves Research Articles

Measurement and Analysis of In Vivo Gastroduodenal Slow Wave Patterns Using Anatomically-Specific Cradles and Electrodes.

Bioelectrical 'slow waves' regulate gastrointestinal contractions. We aimed to confirm whether the pyloric sphincter demarcates slow waves in the intact stomach and duodenum. We developed and validated novel anatomically-specific electrode cradles and analysis techniques which enable high-resolution slow wave mapping across the in vivo gastroduodenal junction. Cradles housed flexible-printed-circuit and custom cradle-specific electrode arrays during acute porcine experiments (N = 9; 44.92 kg ± 8.49 kg) and maintained electrode contact with the gastroduodenal serosa. Simultaneous gastric and duodenal slow waves were filtered independently after determining suitable organ-specific filters. Validated algorithms calculated slow wave propagation patterns and quantitative descriptions. Butterworth filters, with cut-off frequencies (0.0167 - 2) Hz and (0.167 - 3.33) Hz, were optimal filters for gastric and intestinal slow wave signals, respectively. Antral slow waves had a frequency of (2.76 ± 0.37) cpm, velocity of (4.83 ± 0.21) mm·s-1, and amplitude of (1.13 ± 0.24) mV, before terminating at the quiescent pylorus that was (46.54 ± 5.73) mm wide. Duodenal slow waves had a frequency of (18.13 ± 0.56) cpm, velocity of (11.66 ± 1.36) mm·s-1, amplitude of (0.32 ± 0.03) mV, and originated from a pacemaker region (7.24 ± 4.70) mm distal to the quiescent zone. Novel engineering methods enable measurement of in vivo electrical activity across the gastroduodenal junction and provide qualitative and quantitative definitions of slow wave activity. The pylorus is a clinical target for a range of gastrointestinal motility disorders and this work may inform diagnostic and treatment practices.

Effects of new-generation inhibitors of the calcium-activated chloride channel anoctamin 1 on slow waves in the gastrointestinal tract.

High-throughput screening of compound libraries using genetically encoded fluorescent biosensors has identified several second-generation. low MW inhibitors of the calcium-activated chloride channel anoctamin 1 (CaCC/Ano1). Here we have (i) examined the effects of these Ano1 inhibitors on gastric and intestinal pacemaker activity; (ii) compared the effects of these inhibitors with those of the more classical CaCC inhibitor, 5-nitro-2-(3-phenylpropylalanine) benzoate (NPPB); (ii) examined the mode of action of these compounds on the waveform of pacemaker activity; and (iii) compared differences in the sensitivity between gastric and intestinal pacemaker activity to the Ano1 inhibitors. Using intracellular microelectrode recordings of gastric and intestinal muscle preparations from C57BL/6 mice, the dose-dependent effects of Ano1 inhibitors were examined on spontaneous electrical slow waves. The efficacy of second-generation Ano1 inhibitors on gastric and intestinal pacemaker activity differed significantly. Antral slow waves were more sensitive to these inhibitors than intestinal slow waves. CaCCinh -A01 and benzbromarone were the most potent at inhibiting slow waves in both muscle preparations and more potent than NPPB. Dichlorophene and hexachlorophene were equally potent at inhibiting slow waves. Surprisingly, slow waves were relatively insensitive to T16Ainh -A01 in both preparations. We have identified several second-generation Ano1 inhibitors, blocking gastric and intestinal pacemaker activity. Different sensitivities to Ano1 inhibitors between stomach and intestine suggest the possibility of different splice variants in these two organs or the involvement of other conductances in the generation and propagation of pacemaker activity in these tissues.

A New Concept for Pacemaker Activity in the Human Stomach (J Physiol 2011:589[Pt 24];6105-6118)

Rhee et al1 has reported a study entitled Analysis of pacemaker activity in the human stomach in the December issue of Journal of Physiology 2011. Extracellular electrical recording techniques using animal models have contributed to establish important concepts of human gastric physiology.2,3 The electrical quiescence in the gastric fundus, 3 cycles per minute (cpm) pacemaker activity in corpus and antrum, and proximal-to-distal slow wave frequency gradient tended to accept as standard concepts. However, several findings which do not concur with those classic concepts have been presented in Rhee's study. Rhee et al1 experimented using human gastric muscles obtained from patients undergoing gastric resection for gastric cancer and investigated the slow wave pacemaker activity recorded with intracellular microelectrodes, the contractions recorded by isometric force techniques and the distribution of interstitial cells of Cajal (ICC). Interestingly, different from the recent studies, slow waves were routinely recorded from gastric fundic muscles. And similar waveforms as slow waves in more distal regions were presented with couple to phasic contractions. Also gastric slow wave frequency was significantly greater than 3 cpm in all regions of the stomach. Additionally antral slow wave frequency often exceeded the highest frequency of pacemaker activity in the corpus. These observations could not be explained as chronotropic mechanisms such as muscarinic and prostaglandin receptor binding, stretch, extracelluar Ca2+ and temperature. After all, muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution in ICC.

Peripheral Effects of Rimonabant on Upper Gastrointestinal Motility

Background: Rimonabant (SR 141716A) is an antagonist-inverse agonist of cannabinoid receptor 1 (CB1), which was developed for the obesity treatment. The aim of this study was to investigate effects of rimonabant on gastric emptying, gastric tone, accommodation and compliance, antral contractions and small intestinal contractions in dogs. Materials and Methods: Six dogs were equipped with a duodenal cannula for the measurements of gastricemptying, small bowel contractions and small bowel slow waves. Another six dogs were equipped with a gastric cannula for the measurements of gastric tone, accommodation and compliance, antral contractions and gastric slow waves. Each of the measurements was obtained in one control and two rimonabant sessions (different doses). Results: 1) Rimonabant accelerated gastric emptying of liquids and the effect was more potent at a dose of 1 mg/kg than 0.5 mg/kg; 2) Rimonabant increased gastric tone and reduced gastric compliance and accommodation with the 1.0 mg/kg dose being more potent; 3) Rimonabant inhibited antral contractions; 4) Rimonabant increased small intestinal contractions. The small intestinal contraction index was 9.60 ± 2.44 in the control session and increased to 12.35 ± 1.45 with rimonabant 0.5mg/kg (p=0.018 vs. control) and 14.75 ± 2.46 with rimonabant 1 mg/kg (p=0.008 vs. control). Conclusions: Rimonabant reduces gastric compliance and accommodation, inhibits antral contractions but increases intestinal motility. These findings suggest the peripheral mechanisms of rimonabant in reducing food intake and body weight.

Analysis of pacemaker activity in the human stomach

Extracellular electrical recording and studies using animal models have helped establish important concepts of human gastric physiology. Accepted standards include electrical quiescence in the fundus, 3 cycles per minute (cpm) pacemaker activity in corpus and antrum, and a proximal-to-distal slow wave frequency gradient. We investigated slow wave pacemaker activity, contractions and distribution of interstitial cells of Cajal (ICC) in human gastric muscles. Muscles were obtained from patients undergoing gastric resection for cancer, and the anatomical locations of each specimen were mapped by the operating surgeon to 16 standardized regions of the stomach. Electrical slow waves were recorded with intracellular microelectrodes and contractions were recorded by isometric force techniques. Slow waves were routinely recorded from gastric fundus muscles. These events had similar waveforms as slow waves in more distal regions and were coupled to phasic contractions. Gastric slow wave frequency was significantly greater than 3 cpm in all regions of the stomach. Antral slow wave frequency often exceeded the highest frequency of pacemaker activity in the corpus. Chronotropic mechanisms such as muscarinic and prostaglandin receptor binding, stretch, extracelluar Ca(2+) and temperature were unable to explain the observed slow wave frequency that exceeded accepted normal levels. Muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution in ICC we mapped throughout the tunica muscularis. Our findings suggest that extracellular electrical recording has underestimated human slow wave frequency and mechanisms of human gastric function may differ from standard laboratory animal models.

Origin, propagation and regional characteristics of porcine gastric slow wave activity determined by high-resolution mapping

The pig is a popular model for gastric electrophysiology studies. However, its normal baseline gastric activity has not been well characterized. High-resolution (HR) mapping has recently enabled an accurate description of human and canine gastric slow wave activity, and was employed here to define porcine gastric slow wave activity. Fasted pigs underwent HR mapping following anesthesia and laparotomy. Flexible printed-circuit-board arrays were used (160-192 electrodes; spacing 7.62 mm). Anterior and posterior surfaces were mapped simultaneously. Activation times, velocities, amplitudes and frequencies were calculated, and regional differences evaluated. Mean slow wave frequency was 3.22 ± 0.23 cpm. Slow waves propagated isotropically from the pacemaker site (greater curvature, mid-fundus). Pacemaker activity was of higher velocity (13.3 ± 1.0 mm s(-1)) and greater amplitude (1.3 ± 0.2 mV) than distal fundal activity (9.0 ± 0.6 mm s(-1), 0.9 ± 0.1 mV; P < 0.05). Velocities and amplitudes were similar in the distal fundus, proximal corpus (8.4 ± 0.8 mm s(-1), 1.0 ± 0.1 mV), distal corpus (8.3 ± 0.8 mm s(-1), 0.9 ± 0.2 mV) and antrum (6.8 ± 0.6 mm s(-1), 1.1 ± 0.2 mV). Activity was continuous across the anterior and posterior gastric surfaces. This study has quantified normal porcine gastric slow wave activity at HR during anesthesia and laparotomy. The pacemaker region was associated with high-amplitude, high-velocity slow wave activity compared to the activity in the rest of the stomach. The increase in distal antral slow wave velocity and amplitude previously described in canines and humans is not observed in the pig. Investigators should be aware of these inter-species differences.

Gastric Electrical Stimulation with the TANTALUS® System in Obese Type 2 Diabetes Patients: Effect on Weight and Glycemic Control

The TANTALUS System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption. Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 +/- 1 kg/m(2), hemoglobin A1c [HbA1c] 8.5 +/- 0.2%).Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period. Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 +/- 0.7% to 7.6 +/- 1%, p < .01. Weight was also significantly reduced from 107.7 +/- 21.1 to 102.4 +/- 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss (R(2) = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only). Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.

T1792 Modulation of Gastric Antral Slow Waves of Guinea-Pig By Ca2+ Store Inhibitors, Extracellular pH and Acetylcholine

T1792 Modulation of Gastric Antral Slow Waves of Guinea-Pig By Ca2+ Store Inhibitors, Extracellular pH and Acetylcholine

Prostaglandin regulation of gastric slow waves and peristalsis

Gastric emptying depends on functional coupling of slow waves between the corpus and antrum, to allow slow waves initiated in the gastric corpus to propagate to the pyloric sphincter and generate gastric peristalsis. Functional coupling depends on a frequency gradient where slow waves are generated at higher frequency in the corpus and drive the activity of distal pacemakers. Simultaneous intracellular recording from corpus and antrum was used to characterize the effects of PGE(2) on slow waves in the murine stomach. PGE(2) increased slow-wave frequency, and this effect was mimicked by EP(3), but not by EP(2), receptor agonists. Chronotropic effects were due to EP(3) receptors expressed by intramuscular interstitial cells of Cajal because these effects were not observed in W/W(V) mice. Although the integrated chronotropic effects of EP(3) receptor agonists were deduced from electrophysiological experiments, no clear evidence of functional uncoupling was observed with two-point electrical recording. Gastric peristalsis was also monitored by video imaging and spatiotemporal maps to study the impact of chronotropic agonists on propagating contractions. EP(3) receptor agonists increased the frequency of peristaltic contractions and caused ectopic sites of origin and collisions of peristaltic waves. The impact of selective regional application of chronotropic agonists was investigated by use of a partitioned bath. Antral slow waves followed enhanced frequencies induced by stimulation of the corpus, and corpus slow waves followed when slow-wave frequency was elevated in the antrum. This demonstrated reversal of slow-wave propagation with selective antral chronotropic stimulation. These studies demonstrate the impact of chronotropic agonists on regional intrinsic pacemaker frequency and integrated gastric peristalsis.

Synchronized gastric electrical stimulation improves vagotomy-induced impairment in gastric accommodation via the nitrergic pathway in dogs

Impaired gastric accommodation and gastric dysrhythmia are common in gastroparesis and functional dyspepsia. Recent studies have shown that synchronized gastric electrical stimulation (SGES) accelerates gastric emptying and enhances antral contractions in dogs. The aim of this study was to investigate the effects and mechanism of SGES on gastric accommodation and slow waves impaired by vagotomy in dogs. Gastric tone, compliance, and accommodation as well as slow waves with and without SGES were assessed in seven female regular dogs and seven dogs with bilateral truncal vagotomy, chronically implanted with gastric serosal electrodes and a gastric cannula. We found that 1) vagotomy impaired gastric accommodation that was normalized by SGES. The postprandial increase in gastric volume was 283.5 +/- 50.6 ml in the controlled dogs, 155.2 +/- 49.2 ml in the vagotomized dogs, and 304.0 +/- 57.8 ml in the vagotomized dogs with SGES. The ameliorating effect of SGES was no longer observed after application of N(omega)-nitro-L-arginine (L-NNA); 2) vagotomy did not alter gastric compliance whereas SGES improved gastric compliance in the vagotomized dogs, and the improvement was also blocked by L-NNA; and 3) vagotomy impaired antral slow wave rhythmicity in both fasting and fed states. SGES at the proximal stomach enhanced the postprandial rhythmicity and amplitude (dominant power) of the gastric slow waves in the antrum. In conclusion, SGES with appropriate parameters restores gastric accommodation and improves gastric slow waves impaired by vagotomy. The improvement in gastric accommodation with SGES is mediated via the nitrergic pathway. Combined with previously reported findings (enhanced antral contractions and accelerated gastric emptying) and findings in this study (improved gastric accommodation and slow waves), SGES may be a viable therapy for gastroparesis.

Mast Cell–Nerve Interactions in Children With Functional Dyspepsia

Functional dyspepsia in childhood is commonly triggered by food allergen in sensitised individuals. We investigated the topography of eosinophils and mast cells in gastric antral lamina propria, the interaction of mast cell products with mucosal nerve fibres, and changes in gastric antral muscle slow wave activity in children with atopy and non-atopy-related functional dyspepsia. Open label study of gastric mucosal cow's milk challenge in 10 atopic and 6 nonatopic children (ages 2-12 years) investigated consecutively with gastroscopy for functional dyspepsia. Simultaneous surface electrogastrography and milk challenge were undertaken and laser scanning fluorescence microscopy used to examine the association of mast cell tryptase with mucosal nerves in the gastric mucosa before and after challenge. Eosinophils and mast cells within the lamina propria were increased in number in children with atopic functional dyspepsia and degranulated rapidly after cow's milk challenge in the atopic group. For degranulating eosinophils, median = 13.0% (interquartile range = 3.7-31.0) premilk versus 32.0% (12.0-42.0) after milk biopsies (P < 0.05); for degranulating mast cells, 5.35% (2.7-10.9) premilk biopsies versus 18.75% (12.9-22.1) after milk biopsies (P < 0.05). No such differences were seen in nonatopic patients. Mast cells were closely associated with mucosal nerve fibres and released tryptase, which colocalised with proteinase-activated receptors on mucosal nerve fibres. The gastric antral slow wave became abnormal within 2 minutes of antigen challenge in atopics with an increase in dominant frequency instability coefficient (P < 0.005), decrease in 3 cycles per minute myoelectrical activity (P < 0.01), and increase in bradygastria (P < 0.01). Early-onset neuroimmune interactions induced by cow's milk in the gastric mucosa of atopic children are associated with rapid disturbance of gastric myoelectrical activity and dyspeptic symptoms.

The use of gastric electrical signals for algorithm for automatic eating detection in dogs

Food ingestion increases fundic impedance (FI) and reduces antral slow wave rate (SWR). Our aim was to determine if such changes can be integrated into an algorithm for automatic eating detection (AED). When incorporated in implantable medical devices, AED can time treatment to food intake without need for patient input. Four dogs were implanted with fundic and antral electrodes, connected to an implantable recording device. Changes in FI and SWR induced by fixed meals of different weights were determined, and were used to build an AED algorithm. Its performance was then tested on the same animals given an ad libitum access to food. The effects of gastric balloon distension and nitroglycerin on SWR and FI were also tested. Fixed meals reduced SWR in a weight-dependent manner, R(2) = 0.936, P < 0.05 baseline compared to 50, 100, 200 and 400 g. Meals increased FI above baseline in a weight-dependent manner; R(2) = 0.994, P < 0.05 baseline compared to 200 and 400 g. During ad libitum intake, the AED algorithm detected 86% of all meals > or =15 g. Gastric distension reduced SWR and increased FI. Nitroglycerin reduced SWR. AED, using changes in FI and gastric SWR is feasible. Changes in FI and SWR are induced primarily by the presence of food in the stomach.

Effects of Various Doses of Cholecystokinin Octapeptide and Cerulein on Antral Slow-Wave Frequency and Amplitude in Conscious Sheep

It is suspected that cholecystokinin (CCK) might affect antral slow-wave frequency and amplitude, but in sheep this problem is virtually unknown. Therefore the myoelectric activity was continuously recorded before and after intravenous administration of 0.15 M NaCl or CCK peptides in adult rams, equipped with platinum bipolar electrodes in the abomasal antrum, duodenum, and jejunum. CCK octapeptide (CCK-OP) was given to five rams at doses of 17.5, 175, or 1750 pmol/ kg and cerulein was administered to six rams at doses of 0.735, 7.35, or 73.5 pmol/kg of body weight. Each dose was infused to fasted or non-fasted animals for 30, 60, 120, or 300 s during phase 1, 2a or 2b (the less or more intense) of the migrating myoelectric complex (MMC). The 300-sec infusion of the moderate CCK-OP dose during the less intense or more intense phase 2b of the MMC increased the antral slow-wave amplitude from 79 ± 7 to 124 ± 26 μV (p &lt; 0.01) and from 82 ± 8 to 175 ± 40 μV (p &lt; 0.001), respectively. The 300-sec infusion of the highest CCK-OP dose under the same conditions increased antral slow-wave amplitude from 79 ± 6 to 121 ± 24 μV (p &lt; 0.05) and from 84 ± 9 to 138 ± 27 μV (p &lt; 0.01), respectively. Administration of the moderate dose of CCK for 120 s in the course of the less or more intense phase 2b of the MMC increased antral slow-wave frequency from 6.1 ± 0.2 to 6.6 ± 0.4 cpm (N.S.) and from 6.1 ± 0.3 to 6.8 ± 0.4 cpm (p &lt; 0.05), respectively. Administration of the highest dose of CCK-OP for 120 s in the course of the less or more intense phase 2b of the MMC increased the antral slow-wave frequency from 6.2 ± 0.3 to 7.2 ± 0.4 (p &lt; 0.05) and from 6.0 ± 0.3 to 7.8 ± 0.6 cpm (p &lt; 0.001), respectively. It is concluded that CCK in physiological and putatively pharmacological doses can affect the slow-wave frequency and amplitude in sheep related in part to the small-intestinal MMC phase and the intensity of the antral motor activity.

Involvement of interstitial cells of Cajal in the control of smooth muscle excitability

Involvement of interstitial cells of Cajal in the control of smooth muscle excitability

Atypical slow waves generated in gastric corpus provide dominant pacemaker activity in guinea pig stomach

When intracellular recordings were made from the circular layer of the intact muscular wall of the isolated guinea pig gastric corpus, an ongoing regular high frequency discharge of slow waves was detected even though this region lacked myenteric interstitial cells. When slow waves were recorded from preparations consisting of both the antrum and the corpus, slow waves of identical frequency, but with different shapes, were generated in the two regions. Corporal slow waves could be distinguished from antral slow waves by their time courses and amplitudes. Corporal slow waves, like antral slow waves, were abolished by buffering the internal concentration of calcium ions, [Ca2+]i, to low levels, or by caffeine, 2-aminoethoxydiphenyl borate or the chloride channel blocker DIDS. Corporal preparations demonstrated an ongoing discharge of unitary potentials, as has been found in all other tissues containing interstitial cells. The experiments show that the corpus provides the dominant pacemaker activity which entrains activity in other regions of the stomach and it is suggested that this activity is generated by corporal intramuscular interstitial cells.

Pacing of interstitial cells of Cajal in the murine gastric antrum: neurally mediated and direct stimulation.

Phase advancement of electrical slow waves and regulation of pacemaker frequency was investigated in the circular muscle layer of the gastric antra of wild-type and W/W(V) mice. Slow waves in the murine antrum of wild-type animals had an intrinsic frequency of 4.4 cycles min(-1) and were phase advanced and entrained to a maximum of 6.3 cycles min(-1) using 0.1 ms pulses of electrical field stimulation (EFS) (three pulses delivered at 3-30 Hz). Pacing of slow waves was blocked by tetrodotoxin (TTX) and atropine, suggesting phase advancement was mediated via intrinsic cholinergic nerves. Phase advancement and entrainment of slow waves via this mechanism was absent in W/W(V) mutants which lack intramuscular interstitial cells of Cajal (ICC-IM). These data suggest that neural regulation of slow wave frequency and regulation of smooth muscle responses to slow waves are mediated via nerve-ICC-IM interactions. With longer stimulation parameters (1.0-2.0 ms), EFS phase advanced and entrained slow waves in wild-type and W/W(V) animals. Pacing with 1-2 ms pulses was not inhibited by TTX or atropine. These data suggest that stimulation with longer pulse duration is capable of directly activating the pacemaker mechanism in ICC-MY networks. In summary, intrinsic excitatory neurons can phase advance and increase the frequency of antral slow waves. This form of regulation is mediated via ICC-IM. Longer pulse stimulation can directly activate ICC-MY in the absence of ICC-IM.

Influence of Various Feeding Conditions, the Migrating Myoelectric Complex and Cholinergic Drugs on Antral Slow Waves in Sheep

The presented study was designed to elucidate whether the cholinergic mechanisms control ovine antral slow waves in various physiological conditions, including feeding and various phases of migrating myoelectric complex (MMC). The investigations were carried out on six adult sheep of Polish Merino breed with seven bipolar electrodes surgically implanted onto the antral and small intestinal wall. In the course of chronic experiments, the myoelectric activity was recorded from these regions using the multichannel electroencephalograph. Experiments were performed on 48h fasted and non-fasted animals. During some of these experiments, sheep were fed with standard fodder. During control experiments 0.15M NaCl was slowly administered i.v. through the indwelling catheter and during other experiment, hexamethonium bromide (2.0 and 5.0mg/kg), atropine sulfate (0.02; 0.1; 0.5 and 1.5mg/kg) and pirenzepine dihydrochloride (0.02; 0.5 and 2.0mg/kg) were administered i.v. during phase 1-2a or 2b MMC. The drugs were also given in combinations. The recordings were analysed and the antral slow wave amplitudes and frequencies were calculated. Unlike the slow wave amplitude, either feeding or the anticholinergic drugs significantly increased slow wave frequency, especially when the given procedure was started during phase 2b MMC. The most pronounced effects were observed after hexamethonium given alone or in combinations. Thus, the cholinergic system modulates antral slow wave frequency in sheep.

Plasticity of electrical pacemaking by interstitial cells of Cajal and gastric dysrhythmias in W/Wv mutant mice

Background & Aims: Interstitial cells of Cajal (ICC) generate and propagate slow waves in the stomach. Gastric peristalsis depends on a proximal-to-distal gradient in slow wave frequency. We tested whether the gastric frequency gradient was an intrinsic property of ICC and whether dysrhythmias result from disruptions of ICC networks. Methods: We studied wild-type (WT) and W/WV mice, which have only myenteric (pacemaker) ICC in the stomach. ICC distributions were analyzed by Kit immunofluorescence. Pacemaking in tissues was studied by intracellular electrophysiologic recording and in cultured ICC by monitoring mitochondrial [Ca2+] oscillations with rhod-2 fluorescence or membrane potential with DiBAC4(3) fluorescence. Results: Slow wave frequencies were constant throughout WT gastric muscle sheets containing corpus and antrum. Separating the antrum from the corpus caused a significant drop in antral slow wave frequency. ICC from WT antrums also displayed significantly slower pacemaker frequencies than corpus ICC, but the corpus pacemaker frequency dominated in cocultures of corpus and antrum ICC. Myenteric ICC networks were reduced in W/WV mice, particularly in the corpus. In W/WV mice, separating the antrum from the corpus failed to reduce antral slow wave frequency. Antral pacemaker frequency in ICC from W/WV stomachs was the same as in corpus ICC. Conclusions: The proximal-to-distal slow wave frequency gradient and entrainment of distal electrical activity by proximal pacemakers are fundamental properties of gastric ICC. Chronic depletion of ICC networks disrupts the proximal-to-distal frequency gradient, and emergence of ectopic pacemakers in the antrum may be caused by “reprogramming” of the ICC pacemaker apparatus.GASTROENTEROLOGY 2002;123:2028-2040

Corrigendum

Corrigendum

The slow wave does not propagate across the gastroduodenal junction in the isolated feline preparation.

Detailed spatial analysis of the propagation of individual slow waves was performed in the isolated gastroduodenal preparation of the cat. Use was made of a system that allowed the simultaneous recordings from 240 extracellular electrodes, which were positioned across the gastroduodenal region. Reconstructions of the spread of propagation (n = 31) revealed that (a) the antral slow wave never propagated into the duodenum but was blocked at the pyloric ring, (b) the duodenal slow wave did not activate the antral tissue, and (c) a quiescent zone in which no slow waves could be recorded was always present at the most proximal part of the duodenum immediately distal to the pyloric ring. Furthermore, phase density distributions of duodenal cycles revealed that antral activity had no influence on the rate of discharge of duodenal pacemakers. Light microscopic study of sections of the duodenum close to the pyloric ring and further away did not show any structural differences between the quiescent zone and the active areas. In conclusion, slow waves do not propagate across the gastroduodenal junction in the isolated feline preparation and therefore do not seem to play a role in the electro-mechanical integration between the stomach and the duodenum.