Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associate... more Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associated with gas expulsion. Our hypothesis was that the SPW might be a critical component of most colonic motor functions, and hence might act as a biomarker for healthy colon motility. To that end, we performed high-resolution colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced) water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns were recorded during baseline, proximal and rectal balloon distention, after a meal and following proximal and rectal luminal bisacodyl administration. Quantification was performed using software, based on Image J, developed during this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were associated with water or balloon expulsion. SPWs were prominently emerging at the termination of proximal high amplitude propagating pressure waves (HAPWs); we termed this motor pattern HAPW-SPWs; hence, ...
American journal of physiology. Gastrointestinal and liver physiology, Jan 10, 2018
The role of short-chain fatty acids (SCFAs) in colonic motility is controversial. Germ free (GF) ... more The role of short-chain fatty acids (SCFAs) in colonic motility is controversial. Germ free (GF) mice are unable to produce these metabolites and serve as a model to study how their absence affects colonic motility. GF transit is slower than controls and colonization of these mice improves transit and serotonin (5-HT) levels. Our aim was to determine the role SCFAs play in improving transit, and whether this is dependent on mucosal 5-HT signaling. Motility was assessed in GF mice via spatiotemporal mapping using two techniques. The first measured motor patterns under intraluminal perfusion of phosphate buffer (PBS) with or without SCFA. In addition, outflow from the colon was recorded to quantify outflow due to individual propulsive contractions. The second technique measured fecal pellet propulsion using artificial pellets. Motility was then assessed in TPH1 KO mice, devoid of mucosal 5-HT, with PBS, butyrate and propionate intraluminal perfusion. GF mice exhibited a lower proporti...
Background: Chinese university freshmen receive 4-weeks military training that involved moderate ... more Background: Chinese university freshmen receive 4-weeks military training that involved moderate to intense physical exercise. Studies have demonstrated heterogeneous effects of exercise on the autonomic nervous system.Objective: To evaluate the effects of training on the autonomic nervous system noninvasively using electrogastrograms, heart rate variability (HRV), pulse rate, and the sympathetic skin response (SSR).Methods: Twenty freshmen received all assessments in the fasting state and after a standard meal: (1) one week before the training, (2) at the end of the second week of the training, and (3) one week after the training.Results: (1) The training had a significant effect on meal-induced gastric pacemaker activity. Before the training, a standard meal did not increase the dominant frequency of gastric slow waves, but the frequency increased during and after the training; (2) The preprandial high frequency (HF), low frequency (LF), and very low frequency (VLF) components of ...
The interstitial cells of Cajal (ICC) generate electrical oscillations in the gut. Synchronisatio... more The interstitial cells of Cajal (ICC) generate electrical oscillations in the gut. Synchronisation of the ICC population is required for generation of coherent electrical waves ("slow waves") that cause muscular contraction and thereby move gut content. The phase response curve (PRC) is an experimental measure of the dynamical rules governing a population of oscillators, that determine their synchrony, and gives an experimental window onto the state space of the oscillator, its dynamical landscape. We measured the PRC of slow wave contractions in the mouse small intestine by the novel combination of diameter mapping and single pulse electrical field stimulation. Phase change (τ) was measured as a function of old phase (ϕ) and distance from the stimulation electrode (d). Plots of τ(ϕ, d) showed an arrowhead shaped region of phase advance enclosing at its base a phase delay peak. The phase change mirrored the perturbed pattern of contraction waves in response to a pulse. The...
What is the central question of this study? What are the effects of interstitial cells of Cajal (... more What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ...
American Journal of Physiology - Gastrointestinal and Liver Physiology, 2015
The rabbit proximal colon is similar in structure to the human colon. Our objective was to study ... more The rabbit proximal colon is similar in structure to the human colon. Our objective was to study interactions of different rhythmic motor patterns focusing on haustral boundary contractions, which create the haustra, using spatiotemporal mapping of video recordings. Haustral boundary contractions were seen as highly rhythmic circumferential ring contractions that propagated slowly across the proximal colon, preferentially but not exclusively in the anal direction, at ∼0.5 cycles per minute; they were abolished by nerve conduction blockers. When multiple haustral boundary contractions propagated in the opposite direction, they annihilated each other upon encounter. Ripples, myogenic propagating ring contractions at ∼9 cycles per min, induced folding and unfolding of haustral muscle folds, creating an anarchic appearance of contractile activity, with different patterns in the three intertaenial regions. Two features of ripple activity were prominent: frequent changes in propagation di...
The Journal of pharmacology and experimental therapeutics, 1984
The circular muscle layer of the canine colon exhibits omnipresent rhythmic periodic waves of dep... more The circular muscle layer of the canine colon exhibits omnipresent rhythmic periodic waves of depolarization (slow waves), acting as pacemaker activity. The electrophysiological and motor responses of this layer to the muscarinic agonists acetylcholine and carbachol, and to the excitatory peptide substance P, were studied using the sucrose-gap technique. In addition, changes in the contractile activity were examined in organ bath experiments. The slow waves consisted of an initial potential followed by a plateau potential. All substances depolarized the membrane and increased dramatically the duration of the plateau potential resulting in a decrease of the slow wave frequency. In addition, the amplitude of the plateau potential was often increased significantly. Carbachol and substance P readily evoked spiking activity whereas acetylcholine did not. Both spiking activity and the plateau potential generated contractile activity. The prolongation of the slow wave duration caused a pro...
The effect of heptanol on electrical coupling between submucosal circular muscle cells of the dog... more The effect of heptanol on electrical coupling between submucosal circular muscle cells of the dog colon and consequences for slow-wave activity were investigated. Electrotonic potentials showed exponential decay giving a length constant of 2.6 +/- 0.5 mm and a time constant of 157 +/- 48 ms. Heptanol reversibly abolished electrotonic current spread, and subsequently no slow-wave activity was recorded. The length constant decreased to less than 0.2 mm. The input resistance increased from 3 to 36 M omega, suggesting a change from tissue syncytium to electrically isolated cells. D600 (5 X 10(-6) M) also abolished slow wave activity but had opposite effects on electrotonic current spread. The data are consistent with the hypothesis that heptanol reversibly inhibits intercellular coupling, resulting in loss of spread of extracellularly applied current, uncoupling of cells, and loss of pacemaker activity. Regulation of intercellular communication may be important in the control of intesti...
The Journal of pharmacology and experimental therapeutics, 1991
The objective was to determine the existence of a glybenclamide-sensitive K+ conductance in intes... more The objective was to determine the existence of a glybenclamide-sensitive K+ conductance in intestinal smooth muscle, to study a possible role for this conductance in the generation of colonic slow wave type action potentials and to investigate if modification of this conductance could alter the action potentials and hence colonic motility. Intracellular electrical recording techniques were used to study properties of cells from the network of smooth muscle cells and interstitial cells of Cajal at the submucosal border of the circular muscle layer of the canine colon, where colonic pacemaker activity is generated. Cromakalim, dose dependently, hyperpolarized the cells and decreased the duration of the action potential, thereby inhibiting contractile activity. The upstroke amplitude and the action potential frequency remained unaltered. Glybenclamide did not affect any parameter of spontaneous electrical activity but prevented all effects of cromakalim. Cromakalim seems to act throug...
Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associate... more Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associated with gas expulsion. Our hypothesis was that the SPW might be a critical component of most colonic motor functions, and hence might act as a biomarker for healthy colon motility. To that end, we performed high-resolution colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced) water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns were recorded during baseline, proximal and rectal balloon distention, after a meal and following proximal and rectal luminal bisacodyl administration. Quantification was performed using software, based on Image J, developed during this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were associated with water or balloon expulsion. SPWs were prominently emerging at the termination of proximal high amplitude propagating pressure waves (HAPWs); we termed this motor pattern HAPW-SPWs; hence, ...
American journal of physiology. Gastrointestinal and liver physiology, Jan 10, 2018
The role of short-chain fatty acids (SCFAs) in colonic motility is controversial. Germ free (GF) ... more The role of short-chain fatty acids (SCFAs) in colonic motility is controversial. Germ free (GF) mice are unable to produce these metabolites and serve as a model to study how their absence affects colonic motility. GF transit is slower than controls and colonization of these mice improves transit and serotonin (5-HT) levels. Our aim was to determine the role SCFAs play in improving transit, and whether this is dependent on mucosal 5-HT signaling. Motility was assessed in GF mice via spatiotemporal mapping using two techniques. The first measured motor patterns under intraluminal perfusion of phosphate buffer (PBS) with or without SCFA. In addition, outflow from the colon was recorded to quantify outflow due to individual propulsive contractions. The second technique measured fecal pellet propulsion using artificial pellets. Motility was then assessed in TPH1 KO mice, devoid of mucosal 5-HT, with PBS, butyrate and propionate intraluminal perfusion. GF mice exhibited a lower proporti...
Background: Chinese university freshmen receive 4-weeks military training that involved moderate ... more Background: Chinese university freshmen receive 4-weeks military training that involved moderate to intense physical exercise. Studies have demonstrated heterogeneous effects of exercise on the autonomic nervous system.Objective: To evaluate the effects of training on the autonomic nervous system noninvasively using electrogastrograms, heart rate variability (HRV), pulse rate, and the sympathetic skin response (SSR).Methods: Twenty freshmen received all assessments in the fasting state and after a standard meal: (1) one week before the training, (2) at the end of the second week of the training, and (3) one week after the training.Results: (1) The training had a significant effect on meal-induced gastric pacemaker activity. Before the training, a standard meal did not increase the dominant frequency of gastric slow waves, but the frequency increased during and after the training; (2) The preprandial high frequency (HF), low frequency (LF), and very low frequency (VLF) components of ...
The interstitial cells of Cajal (ICC) generate electrical oscillations in the gut. Synchronisatio... more The interstitial cells of Cajal (ICC) generate electrical oscillations in the gut. Synchronisation of the ICC population is required for generation of coherent electrical waves ("slow waves") that cause muscular contraction and thereby move gut content. The phase response curve (PRC) is an experimental measure of the dynamical rules governing a population of oscillators, that determine their synchrony, and gives an experimental window onto the state space of the oscillator, its dynamical landscape. We measured the PRC of slow wave contractions in the mouse small intestine by the novel combination of diameter mapping and single pulse electrical field stimulation. Phase change (τ) was measured as a function of old phase (ϕ) and distance from the stimulation electrode (d). Plots of τ(ϕ, d) showed an arrowhead shaped region of phase advance enclosing at its base a phase delay peak. The phase change mirrored the perturbed pattern of contraction waves in response to a pulse. The...
What is the central question of this study? What are the effects of interstitial cells of Cajal (... more What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ...
American Journal of Physiology - Gastrointestinal and Liver Physiology, 2015
The rabbit proximal colon is similar in structure to the human colon. Our objective was to study ... more The rabbit proximal colon is similar in structure to the human colon. Our objective was to study interactions of different rhythmic motor patterns focusing on haustral boundary contractions, which create the haustra, using spatiotemporal mapping of video recordings. Haustral boundary contractions were seen as highly rhythmic circumferential ring contractions that propagated slowly across the proximal colon, preferentially but not exclusively in the anal direction, at ∼0.5 cycles per minute; they were abolished by nerve conduction blockers. When multiple haustral boundary contractions propagated in the opposite direction, they annihilated each other upon encounter. Ripples, myogenic propagating ring contractions at ∼9 cycles per min, induced folding and unfolding of haustral muscle folds, creating an anarchic appearance of contractile activity, with different patterns in the three intertaenial regions. Two features of ripple activity were prominent: frequent changes in propagation di...
The Journal of pharmacology and experimental therapeutics, 1984
The circular muscle layer of the canine colon exhibits omnipresent rhythmic periodic waves of dep... more The circular muscle layer of the canine colon exhibits omnipresent rhythmic periodic waves of depolarization (slow waves), acting as pacemaker activity. The electrophysiological and motor responses of this layer to the muscarinic agonists acetylcholine and carbachol, and to the excitatory peptide substance P, were studied using the sucrose-gap technique. In addition, changes in the contractile activity were examined in organ bath experiments. The slow waves consisted of an initial potential followed by a plateau potential. All substances depolarized the membrane and increased dramatically the duration of the plateau potential resulting in a decrease of the slow wave frequency. In addition, the amplitude of the plateau potential was often increased significantly. Carbachol and substance P readily evoked spiking activity whereas acetylcholine did not. Both spiking activity and the plateau potential generated contractile activity. The prolongation of the slow wave duration caused a pro...
The effect of heptanol on electrical coupling between submucosal circular muscle cells of the dog... more The effect of heptanol on electrical coupling between submucosal circular muscle cells of the dog colon and consequences for slow-wave activity were investigated. Electrotonic potentials showed exponential decay giving a length constant of 2.6 +/- 0.5 mm and a time constant of 157 +/- 48 ms. Heptanol reversibly abolished electrotonic current spread, and subsequently no slow-wave activity was recorded. The length constant decreased to less than 0.2 mm. The input resistance increased from 3 to 36 M omega, suggesting a change from tissue syncytium to electrically isolated cells. D600 (5 X 10(-6) M) also abolished slow wave activity but had opposite effects on electrotonic current spread. The data are consistent with the hypothesis that heptanol reversibly inhibits intercellular coupling, resulting in loss of spread of extracellularly applied current, uncoupling of cells, and loss of pacemaker activity. Regulation of intercellular communication may be important in the control of intesti...
The Journal of pharmacology and experimental therapeutics, 1991
The objective was to determine the existence of a glybenclamide-sensitive K+ conductance in intes... more The objective was to determine the existence of a glybenclamide-sensitive K+ conductance in intestinal smooth muscle, to study a possible role for this conductance in the generation of colonic slow wave type action potentials and to investigate if modification of this conductance could alter the action potentials and hence colonic motility. Intracellular electrical recording techniques were used to study properties of cells from the network of smooth muscle cells and interstitial cells of Cajal at the submucosal border of the circular muscle layer of the canine colon, where colonic pacemaker activity is generated. Cromakalim, dose dependently, hyperpolarized the cells and decreased the duration of the action potential, thereby inhibiting contractile activity. The upstroke amplitude and the action potential frequency remained unaltered. Glybenclamide did not affect any parameter of spontaneous electrical activity but prevented all effects of cromakalim. Cromakalim seems to act throug...
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