scholarly journals Engaging Biological Oscillators through Second Messenger Pathways Permits Emergence of a Robust Gastric Slow-Wave during Peristalsis

2021 ◽  
Author(s):  
Md Ashfaq Ahmed ◽  
Sharmila Venugopal ◽  
Ranu Jung
Keyword(s):  
Slow Wave ◽  
Gastric Motility ◽  
Second Messengers ◽  
Mechanistic Explanation ◽  
Theoretical Work ◽  
Slow Waves ◽  
Intercellular Coupling ◽  
Motility Disorders ◽  
Gastric Slow Wave ◽  
Biological Oscillators

Peristalsis, the coordinated contraction-relaxation of the muscles of the stomach, is important for normal gastric motility and is impaired in motility disorders. Coordinated electrical depolarizations that originate and propagate within a network of interconnected layers of interstitial cells of Cajal (ICC) and smooth muscle (SM) cells of the stomach wall as a slow-wave, underly peristalsis. Normally, the gastric slow-wave oscillates with a single period and uniform rostrocaudal lag, exhibiting network entrainment. Understanding of the integrative role of neurotransmission and intercellular coupling in the propagation of an entrained gastric slow-wave, important for understanding motility disorders, however, remains incomplete. Using a computational framework constituted of a novel gastric motility network (GMN) model we address the hypothesis that engaging biological oscillators (i.e., ICCs) by constitutive gap junction coupling mechanisms and enteric neural stimulus activated signals can confer a robust entrained gastric slow-wave. We demonstrate that while a decreasing enteric neural stimulus gradient that modulates the intracellular IP3 concentration in the ICCs can guide the aboral slow-wave propagation essential for peristalsis, engaging ICCs by recruiting the exchange of second messengers (inositol trisphosphate (IP3) and Ca2+) ensures a robust entrained longitudinal slow-wave, even in the presence of biological variability in coupling strengths. Our GMN with the distinct intercellular coupling in conjunction with the intracellular feedback pathways and a rostrocaudal enteric neural stimulus gradient allows gastric slow waves to oscillate with a moderate range of frequencies and to propagate with a broad range of velocities, thus preventing decoupling observed in motility disorders. Overall, the findings provide a mechanistic explanation for the emergence of decoupled slow waves associated with motility impairments of the stomach, offer directions for future experiments and theoretical work, and can potentially aid in the design of new interventional pharmacological and neuromodulation device treatments for addressing gastric motility disorders.

scholarly journals Engaging biological oscillators through second messenger pathways permits emergence of a robust gastric slow-wave during peristalsis

2021 ◽  
Vol 17 (12) ◽  
pp. e1009644
Author(s):  
Md Ashfaq Ahmed ◽  
Sharmila Venugopal ◽  
Ranu Jung
Keyword(s):  
Slow Wave ◽  
Gastric Motility ◽  
Electrical Coupling ◽  
Mechanistic Explanation ◽  
Theoretical Work ◽  
Slow Waves ◽  
Intercellular Coupling ◽  
Motility Disorders ◽  
Gastric Slow Wave ◽  
Biological Oscillators

Peristalsis, the coordinated contraction—relaxation of the muscles of the stomach is important for normal gastric motility and is impaired in motility disorders. Coordinated electrical depolarizations that originate and propagate within a network of interconnected layers of interstitial cells of Cajal (ICC) and smooth muscle (SM) cells of the stomach wall as a slow-wave, underly peristalsis. Normally, the gastric slow-wave oscillates with a single period and uniform rostrocaudal lag, exhibiting network entrainment. Understanding of the integrative role of neurotransmission and intercellular coupling in the propagation of an entrained gastric slow-wave, important for understanding motility disorders, however, remains incomplete. Using a computational framework constituted of a novel gastric motility network (GMN) model we address the hypothesis that engaging biological oscillators (i.e., ICCs) by constitutive gap junction coupling mechanisms and enteric neural innervation activated signals can confer a robust entrained gastric slow-wave. We demonstrate that while a decreasing enteric neural innervation gradient that modulates the intracellular IP3 concentration in the ICCs can guide the aboral slow-wave propagation essential for peristalsis, engaging ICCs by recruiting the exchange of second messengers (inositol trisphosphate (IP3) and Ca2+) ensures a robust entrained longitudinal slow-wave, even in the presence of biological variability in electrical coupling strengths. Our GMN with the distinct intercellular coupling in conjunction with the intracellular feedback pathways and a rostrocaudal enteric neural innervation gradient allows gastric slow waves to oscillate with a moderate range of frequencies and to propagate with a broad range of velocities, thus preventing decoupling observed in motility disorders. Overall, the findings provide a mechanistic explanation for the emergence of decoupled slow waves associated with motility impairments of the stomach, offer directions for future experiments and theoretical work, and can potentially aid in the design of new interventional pharmacological and neuromodulation device treatments for addressing gastric motility disorders.

scholarly journals Abnormal gastric slow waves in patients with functional dyspepsia assessed by multichannel electrogastrography

2001 ◽  
Vol 280 (6) ◽  
pp. G1370-G1375 ◽  
Author(s):  
Xuemei Lin ◽  
Jiande Z. Chen
Keyword(s):  
Wave Propagation ◽  
Functional Dyspepsia ◽  
Slow Wave ◽  
Single Channel ◽  
Slow Waves ◽  
Lower Percentage ◽  
Healthy Controls ◽  
Fasting State ◽  
Gastric Slow Wave ◽  
Gastric Slow Waves

The aim of this study was to utilize multichannel electrogastrography to investigate whether patients with functional dyspepsia had impaired propagation or coordination of gastric slow waves in the fasting state compared with healthy controls. The study was performed in 10 patients with functional dyspepsia and 11 healthy subjects. Gastric myoelectrical activity was measured by using surface electrogastrography with a specially designed four-channel device. The study was performed for 30 min or more in the fasting state. Special computer programs were developed for the computation of the propagation and coupling of the gastric slow wave. It was found that, compared with the healthy controls, the patients showed a significantly lower percentage of slow wave propagation (58.0 ± 8.9 vs. 89.9 ± 2.6%, P < 0.002) and a significantly lower percentage of slow wave coupling (46.9 ± 4.4 vs. 61.5 ± 6.9%, P < 0.04). In addition, the patients showed inconsistencies in the frequency and regularity of the gastric slow wave among the four-channel electrogastrograms (EGGs). It was concluded that patients with functional dyspepsia have impaired slow wave propagation and coupling. Multichannel EGG has more information than single-channel EGG for the detection of gastric myoelectrical abnormalities.

scholarly journals High-resolution mapping of gastric slow-wave recovery profiles: biophysical model, methodology, and demonstration of applications

2017 ◽  
Vol 313 (3) ◽  
pp. G265-G276 ◽  
Author(s):  
N. Paskaranandavadivel ◽  
L. K. Cheng ◽  
P. Du ◽  
J. M. Rogers ◽  
G. O’Grady
Keyword(s):  
Wave Propagation ◽  
Wavelet Transform ◽  
High Resolution ◽  
Slow Wave ◽  
Recovery Phase ◽  
Slow Waves ◽  
Gastric Slow Wave ◽  
High Resolution Mapping ◽  
Resolution Mapping ◽  
Extracellular Potentials

Slow waves play a central role in coordinating gastric motor activity. High-resolution mapping of extracellular potentials from the stomach provides spatiotemporal detail on normal and dysrhythmic slow-wave patterns. All mapping studies to date have focused exclusively on tissue activation; however, the recovery phase contains vital information on repolarization heterogeneity, the excitable gap, and refractory tail interactions but has not been investigated. Here, we report a method to identify the recovery phase in slow-wave mapping data. We first developed a mathematical model of unipolar extracellular potentials that result from slow-wave propagation. These simulations showed that tissue repolarization in such a signal is defined by the steepest upstroke beyond the activation phase (activation was defined by accepted convention as the steepest downstroke). Next, we mapped slow-wave propagation in anesthetized pigs by recording unipolar extracellular potentials from a high-resolution array of electrodes on the serosal surface. Following the simulation result, a wavelet transform technique was applied to detect repolarization in each signal by finding the maximum positive slope beyond activation. Activation-recovery (ARi) and recovery-activation (RAi) intervals were then computed. We hypothesized that these measurements of recovery profile would differ for slow waves recorded during normal and spatially dysrhythmic propagation. We found that the ARi of normal activity was greater than dysrhythmic activity (5.1 ± 0.8 vs. 3.8 ± 0.7 s; P < 0.05), whereas RAi was lower (9.7 ± 1.3 vs. 12.2 ± 2.5 s; P < 0.05). During normal propagation, RAi and ARi were linearly related with negative unit slope indicating entrainment of the entire mapped region. This relationship was weakened during dysrhythmia (slope: −0.96 ± 0.2 vs −0.71 ± 0.3; P < 0.05). NEW & NOTEWORTHY The theoretical basis of the extracellular gastric slow-wave recovery phase was defined using mathematical modeling. A novel technique utilizing the wavelet transform was developed and validated to detect the extracellular slow-wave recovery phase. In dysrhythmic wavefronts, the activation-to-recovery interval (ARi) was shorter and recovery-to-activation interval (RAi) was longer compared with normal wavefronts. During normal activation, RAi vs. ARi had a slope of −1, whereas the weakening of the slope indicated a dysrhythmic propagation.

Quantitative cellular description of gastric slow wave activity

2008 ◽  
Vol 294 (4) ◽  
pp. G989-G995 ◽  
Author(s):  
Alberto Corrias ◽  
Martin L. Buist
Keyword(s):  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Quantitative Description ◽  
Wave Activity ◽  
Slow Waves ◽  
Slow Wave Activity ◽  
Good Correspondence ◽  
Gastric Slow Wave ◽  
Intracellular Ca ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) are responsible for the spontaneous and omnipresent electrical activity in the stomach. A quantitative description of the intracellular processes whose coordinated activity is believed to generate electrical slow waves has been developed and is presented here. In line with recent experimental evidence, the model describes how the interplay between the mitochondria and the endoplasmic reticulum in cycling intracellular Ca2+ provides the primary regulatory signal for the initiation of the slow wave. The major ion channels that have been identified as influencing slow wave activity have been modeled according to data obtained from isolated ICC. The model has been validated by comparing the simulated profile of the slow waves with experimental recordings and shows good correspondence in terms of frequency, amplitude, and shape in both control and pharmacologically altered conditions.

Mechanisms of burn-induced impairment in gastric slow waves and emptying in rats

2010 ◽  
Vol 299 (1) ◽  
pp. R298-R305 ◽  
Author(s):  
Hanaa S. Sallam ◽  
Hermes M. Oliveira ◽  
Suhuan Liu ◽  
Jiande D. Z. Chen
Keyword(s):  
Gastric Emptying ◽  
Slow Wave ◽  
Delayed Gastric Emptying ◽  
Burn Injury ◽  
Wave Activity ◽  
Cyclooxygenase 2 ◽  
Slow Waves ◽  
Gastric Slow Wave ◽  
Gastric Slow Waves ◽  
Gastric Dysrhythmias

Delayed gastric emptying is common following severe large cutaneous burns; however, the mechanisms of burn-induced delayed gastric emptying remain unknown. The aim of this study was to explore the possible involvement of hyperglycemia and cyclooxygenase-2 receptors in the burn-induced gastric dysrhythmias. Gastric slow waves and gastric emptying were assessed in rats 6 h following sham or burn injury. Animals were randomized to one sham-burn and seven burn groups: untreated; two groups of saline treated (control); insulin treated (5 IU/kg); cyclooxygenase-2 inhibitor treated (10 mg/kg); ghrelin treated (2 nmol/rat); and gastric electrical stimulation treated. It was found that 1) severe burn injury impaired gastric slow waves postprandially and delayed gastric emptying; 2) the impairment in gastric slow waves included a decrease in the slow-wave frequency and in the percentage of normal slow waves, and an increase in the percentage of bradygastria ( P = 0.001, 0.01, and 0.01, respectively vs. preburn values). None of the gastric slow-wave parameters was significantly correlated with gastric emptying; 3) cyclooxygenase-2 inhibitor normalized burn-induced delayed gastric emptying ( P = 0.3 vs. sham-burn), but not gastric dysrhythmias ( P < 0.002 vs. sham), whereas insulin normalized both gastric emptying ( P = 0.4 vs. sham-burn) and gastric dysrhythmias ( P = 0.3 vs. sham-burn); 4) both gastric electrical stimulation and ghrelin accelerated burn-induced delayed gastric emptying ( P = 0.002 and 0.04, respectively, vs. untreated burn). In conclusion, hyperglycemia alters gastric slow-wave activity and delayed gastric emptying, while cyclooxygenase-2 inhibition delays gastric emptying without altering gastric slow-wave activity.

Effects of pacing parameters on entrainment of gastric slow waves in patients with gastroparesis

1998 ◽  
Vol 274 (1) ◽  
pp. G186-G191 ◽  
Author(s):  
Z. Y. Lin ◽  
R. W. McCallum ◽  
B. D. Schirmer ◽  
J. D. Z. Chen
Keyword(s):  
Slow Wave ◽  
Pulse Width ◽  
Cardiac Pacing ◽  
Slow Waves ◽  
Effective Parameters ◽  
Gastric Pacing ◽  
Gastric Slow Wave ◽  
Gastric Slow Waves ◽  
Baseline Recording ◽  
Ectopic Pacemaker

The aim of this study was to investigate the effect of pacing parameters on the entrainment of gastric slow waves in patients with gastroparesis. Four pairs of cardiac pacing wires were placed on the serosal surface of the stomach in 13 patients with gastroparesis. After a baseline recording for 30 min, gastric pacing was performed in a number of sessions with different effective parameters, each lasting for 30 min. The following parameters were found to be effective for the entrainment of the gastric slow wave: a pacing frequency 10% higher than the intrinsic gastric slow wave frequency (IGF), 300 ms pulse width, and 4 mA pacing amplitude. A reduction of pacing amplitude from 4 to 2 mA and 1 mA reduced the percentage of entrainment of the gastric slow wave to 79 ± 10% and 50 ± 11%, respectively. Pacing with a pulse width of 30 or 3 ms was not able to entrain the gastric slow wave in any of the patients. An ectopic pacemaker of tachygastria found in three patients was reversed with gastric pacing. It was concluded that gastric pacing at a frequency up to 10% higher than the IGF and with an amplitude of 4 mA and a pulse width of 300 ms is able to completely entrain the gastric slow wave and normalize gastric dysrhythmias in patients with gastroparesis.

Serosal and cutaneous recordings of gastric myoelectrical activity in patients with gastroparesis

1994 ◽  
Vol 266 (1) ◽  
pp. G90-G98 ◽  
Author(s):  
J. D. Chen ◽  
B. D. Schirmer ◽  
R. W. McCallum
Keyword(s):  
Electrical Stimulation ◽  
Slow Wave ◽  
Test Meal ◽  
Frequency Change ◽  
Fasting State ◽  
Gastric Myoelectrical Activity ◽  
Myoelectrical Activity ◽  
Gastric Slow Wave ◽  
Student’S T ◽  
Student’S T Test

The aims of this study were to 1) investigate gastric myoelectrical activity in patients with gastroparesis, 2) validate the cutaneous electrogastrogram (EGG) in tracking the frequency change of the gastric slow wave, and 3) investigate the effect of electrical stimulation on gastric myoelectrical activity. Gastric myoelectrical activity was recorded in 12 patients with documented gastroparesis using serosal electrodes for > 200 min in each subject. All recordings were made at least 4 days after surgery. Each session consisted of a 30-min recording in the fasting state and a 30-min recording after a test meal. The test meal (liquid or mixed) was selected according to patient's tolerance. Electrical stimulation was performed in three subjects via the serosal electrodes at a frequency of 3 cycles/min. Gastric myoelectrical activity was recorded using serosal electrodes in each session. The serosal recording showed slow waves of 2.5 to 4.0 cycles/min in all 12 subjects. Absence of spikes was noted in 11 of the 12 subjects. The simultaneous serosal and cutaneous recording of gastric myoelectrical activity showed that the frequency of the EGG was exactly the same as that of the serosal recording. Liquid meals resulted in a significant decrease in slow-wave frequency (Student's t test, P = 0.006), and the EGG accurately reflected this change. Electrical stimulation had no effect on the frequency of the gastric slow wave and did not induce spikes.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Aging Slow Wave: A Shifting Amalgam of Distinct Slow Wave and Spindle Coupling Subtypes Define Slow Wave Sleep Across the Human Lifespan

SLEEP ◽  
2021 ◽  
Author(s):  
Brice V McConnell ◽  
Eugene Kronberg ◽  
Peter D Teale ◽  
Stefan H Sillau ◽  
Grace M Fishback ◽  
...  
Keyword(s):  
Slow Wave ◽  
Neurological Disease ◽  
Mixed Model ◽  
Slow Wave Sleep ◽  
Sleep Stage ◽  
Slow Waves ◽  
Cross Sectional ◽  
Relative Contribution ◽  
Human Lifespan ◽  
Development And Aging

Abstract Study Objectives Slow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan. Methods Coupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6-88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles. Results Two different subtypes of spindles were identified during the upstates of (distinct) slow waves: an “early-fast” spindle, more common in stage N2 sleep, and a “late-fast” spindle, more common in stage N3. We further found stages N2 and N3 sleep contain a mixture of discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails with increasing age. Conclusions Distinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease.

Sign in / Sign up

Export Citation Format

Share Document