Jan D Huizinga - Profile on Academia.edu (original) (raw)
Papers by Jan D Huizinga
Digestive Diseases and Sciences
Frontiers in Physiology
Background/Aims: Luminal factors such as short-chain fatty acids are increasingly recognized for ... more Background/Aims: Luminal factors such as short-chain fatty acids are increasingly recognized for playing a regulatory role in peristaltic activity. Our objective was to understand the roles of butyrate and propionate in regulating peristaltic activity in relation to distention-induced activities. Methods: Butyrate and propionate were perfused intraluminally under varying intraluminal pressures in murine colons bathed in Krebs solution. We used video recording and spatiotemporal maps to examine peristalsis induced by the intrinsic rhythmic colonic motor complex (CMC) as well as pellet-induced peristaltic reflex movements. Results: The CMC showed several configurations at different levels of excitation, culminating in long distance contractions (LDCs) which possess a triangular shape in murine colon spatiotemporal maps. Butyrate increased the frequency of CMCs but was a much weaker stimulus than distention and only contributed to significant changes under low distention. Propionate inhibited CMCs by decreasing either their amplitudes or frequencies, but only in low distention conditions. Butyrate did not consistently counteract propionate-induced inhibition likely due to the multiple and distinct mechanisms of action for these signaling molecules in the lumen. Pellet movement occurred through ongoing CMCs as well as pellet induced peristaltic reflex movements and butyrate augmented both types of peristaltic motor patterns to decrease the amount of time required to expel each pellet. Conclusions: Butyrate is effective in promoting peristalsis, but only when the level of colonic activity is low such as under conditions of low intraluminal pressure. This suggests that it may play a significant role in patients with poor fiber intake, where there is low mechanical stimulation in the lumen.
Journal of Smooth Muscle Research
Gastrointestinal smooth muscle research has evolved from studies on muscle strips to spatiotempor... more Gastrointestinal smooth muscle research has evolved from studies on muscle strips to spatiotemporal mapping of whole organ motor and electrical activities. Decades of research on single muscle cells and small sections of isolated musculature from animal models has given us the groundwork for interpretation of human in vivo studies. Human gut motility studies have dramatically improved by high-resolution manometry and high-resolution electrophysiology. The details that emerge from spatiotemporal mapping of high-resolution data are now of such quality that hypotheses can be generated as to the physiology (in healthy subjects) and pathophysiology (in patients) of gastrointestinal (dys) motility. Such interpretation demands understanding of the musculature as a super-network of excitable cells (neurons, smooth muscle cells, other accessory cells) and oscillatory cells (the pacemaker interstitial cells of Cajal), for which mathematical modeling becomes essential. The developing deeper understanding of gastrointestinal motility will bring us soon to a level of precision in diagnosis of dysfunction that is far beyond what is currently available.
Intraluminal prucalopride increases propulsive motor activities via luminal 5‐HT 4 receptors in the rabbit colon
Neurogastroenterology & Motility
Pacemaker network properties determine intestinal motor pattern behaviour
Experimental Physiology
Noradrenaline inhibits neurogenic propulsive motor patterns but not neurogenic segmenting haustral progression in the rabbit colon
Neurogastroenterology & Motility
Frontiers in physiology, 2018
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, ...
Molecular Pain
Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pa... more Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Ab sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain. Neuropathic pain model rats were induced with a polyethylene cuff implanted around a sciatic nerve. Cancer-induced pain model rats were induced with mammary rat metastasis tumour-1 rat breast cancer or MATLyLu rat prostate cancer cells implanted into the distal epiphysis of a femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Ab-fibre low threshold mechanoreceptor neurons in both cancer-induced pain and neuropathic pain models exhibited slower dynamics of action potential genesis, including a wider action potential duration and lower action potential amplitude compared to those in control animals. Enhanced excitability of Ab-fibre low threshold mechanoreceptor neurons was also observed in cancer-induced pain and neuropathic pain models. Furthermore, both cancer-induced pain and neuropathic pain models showed abundant abnormal axonal sprouting in bundles of myelinated axons in the ipsilateral spinal laminae IV and V. The patterns of changes show consistency between rat models of cancer-induced pain and neuropathic pain. These findings add to the body of evidence that animal models of cancer-induced pain and neuropathic pain share features that may contribute to the peripheral and central sensitization and tactile hypersensitivity in both pain states.
Abnormal Absorptive Colonic Motor Activity in Germ Free Mice is Rectified by Butyrate, an Effect Possibly Mediated by Mucosal Serotonin
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...
Physiological reports, 2018
Digestive diseases and sciences, Jan 7, 2018
Asian Biomedicine
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 ...
PAIN Reports
Introduction: Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in senso... more Introduction: Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in sensory function. In a previous investigation of an animal model of CIBP, we have observed that changes in intrinsic membrane properties and excitability of dorsal root ganglion (DRG) nociceptive neurons correspond to mechanical allodynia and hyperalgesia. Objectives: To investigate the mechanisms underlying changes in nonnociceptive sensory neurons in this model, we have compared the electrophysiological properties of primary nonnociceptive sensory neurons at ,1 and .2 weeks after CIBP model induction with properties in sham control animals. Methods: Copenhagen rats were injected with 10 6 MAT-LyLu rat prostate cancer cells into the distal femur epiphysis to generate a model of CIBP. After von Frey tactile measurement of mechanical withdrawal thresholds, the animals were prepared for acute electrophysiological recordings of mechanically sensitive neurons in the DRG in vivo. Results: The mechanical withdrawal threshold progressively decreased in CIBP model rats. At ,1 week after model induction, there were no changes observed in nonnociceptive Ab-fiber DRG neurons between CIBP model rats and sham rats. However, at .2 weeks, the Ab-fiber low-threshold mechanoreceptors (LTMs) in CIBP model rats exhibited a slowing of the dynamics of action potential (AP) genesis, including wider AP duration and lower AP amplitude compared with sham rats. Furthermore, enhanced excitability of Ab-fiber LTM neurons was observed as an excitatory discharge in response to intracellular injection of depolarizing current into the soma. Conclusion: After induction of the CIBP model, Ab-fiber LTMs at .2 weeks but not ,1 week had undergone changes in electrophysiological properties. Importantly, changes observed are consistent with observations in models of peripheral neuropathy. Thus, Ab-fiber nonnociceptive primary sensory neurons might be involved in the peripheral sensitization and tumorinduced tactile hypersensitivity in CIBP.
Simultaneous Pressure Waves are an Essential Component of Human Colon Motor Function Assessment, Using High-resolution Manometry
Gastroenterology
Experimental physiology, Sep 3, 2017
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...
Experimental physiology, Mar 30, 2016
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 ...
Haustral boundary contractions in the proximal 3-taeniated rabbit colon
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...
Electrophysiological basis of excitation of canine colonic circular muscle by cholinergic agents and substance P
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...
Electrical coupling and pacemaker activity in colonic smooth muscle
The American journal of physiology, 1988
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...
Potassium channel activation by cromakalim affects the slow wave type action potential of colonic smooth muscle
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...
Digestive Diseases and Sciences
Frontiers in Physiology
Background/Aims: Luminal factors such as short-chain fatty acids are increasingly recognized for ... more Background/Aims: Luminal factors such as short-chain fatty acids are increasingly recognized for playing a regulatory role in peristaltic activity. Our objective was to understand the roles of butyrate and propionate in regulating peristaltic activity in relation to distention-induced activities. Methods: Butyrate and propionate were perfused intraluminally under varying intraluminal pressures in murine colons bathed in Krebs solution. We used video recording and spatiotemporal maps to examine peristalsis induced by the intrinsic rhythmic colonic motor complex (CMC) as well as pellet-induced peristaltic reflex movements. Results: The CMC showed several configurations at different levels of excitation, culminating in long distance contractions (LDCs) which possess a triangular shape in murine colon spatiotemporal maps. Butyrate increased the frequency of CMCs but was a much weaker stimulus than distention and only contributed to significant changes under low distention. Propionate inhibited CMCs by decreasing either their amplitudes or frequencies, but only in low distention conditions. Butyrate did not consistently counteract propionate-induced inhibition likely due to the multiple and distinct mechanisms of action for these signaling molecules in the lumen. Pellet movement occurred through ongoing CMCs as well as pellet induced peristaltic reflex movements and butyrate augmented both types of peristaltic motor patterns to decrease the amount of time required to expel each pellet. Conclusions: Butyrate is effective in promoting peristalsis, but only when the level of colonic activity is low such as under conditions of low intraluminal pressure. This suggests that it may play a significant role in patients with poor fiber intake, where there is low mechanical stimulation in the lumen.
Journal of Smooth Muscle Research
Gastrointestinal smooth muscle research has evolved from studies on muscle strips to spatiotempor... more Gastrointestinal smooth muscle research has evolved from studies on muscle strips to spatiotemporal mapping of whole organ motor and electrical activities. Decades of research on single muscle cells and small sections of isolated musculature from animal models has given us the groundwork for interpretation of human in vivo studies. Human gut motility studies have dramatically improved by high-resolution manometry and high-resolution electrophysiology. The details that emerge from spatiotemporal mapping of high-resolution data are now of such quality that hypotheses can be generated as to the physiology (in healthy subjects) and pathophysiology (in patients) of gastrointestinal (dys) motility. Such interpretation demands understanding of the musculature as a super-network of excitable cells (neurons, smooth muscle cells, other accessory cells) and oscillatory cells (the pacemaker interstitial cells of Cajal), for which mathematical modeling becomes essential. The developing deeper understanding of gastrointestinal motility will bring us soon to a level of precision in diagnosis of dysfunction that is far beyond what is currently available.
Intraluminal prucalopride increases propulsive motor activities via luminal 5‐HT 4 receptors in the rabbit colon
Neurogastroenterology & Motility
Pacemaker network properties determine intestinal motor pattern behaviour
Experimental Physiology
Noradrenaline inhibits neurogenic propulsive motor patterns but not neurogenic segmenting haustral progression in the rabbit colon
Neurogastroenterology & Motility
Frontiers in physiology, 2018
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, ...
Molecular Pain
Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pa... more Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Ab sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain. Neuropathic pain model rats were induced with a polyethylene cuff implanted around a sciatic nerve. Cancer-induced pain model rats were induced with mammary rat metastasis tumour-1 rat breast cancer or MATLyLu rat prostate cancer cells implanted into the distal epiphysis of a femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Ab-fibre low threshold mechanoreceptor neurons in both cancer-induced pain and neuropathic pain models exhibited slower dynamics of action potential genesis, including a wider action potential duration and lower action potential amplitude compared to those in control animals. Enhanced excitability of Ab-fibre low threshold mechanoreceptor neurons was also observed in cancer-induced pain and neuropathic pain models. Furthermore, both cancer-induced pain and neuropathic pain models showed abundant abnormal axonal sprouting in bundles of myelinated axons in the ipsilateral spinal laminae IV and V. The patterns of changes show consistency between rat models of cancer-induced pain and neuropathic pain. These findings add to the body of evidence that animal models of cancer-induced pain and neuropathic pain share features that may contribute to the peripheral and central sensitization and tactile hypersensitivity in both pain states.
Abnormal Absorptive Colonic Motor Activity in Germ Free Mice is Rectified by Butyrate, an Effect Possibly Mediated by Mucosal Serotonin
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...
Physiological reports, 2018
Digestive diseases and sciences, Jan 7, 2018
Asian Biomedicine
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 ...
PAIN Reports
Introduction: Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in senso... more Introduction: Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in sensory function. In a previous investigation of an animal model of CIBP, we have observed that changes in intrinsic membrane properties and excitability of dorsal root ganglion (DRG) nociceptive neurons correspond to mechanical allodynia and hyperalgesia. Objectives: To investigate the mechanisms underlying changes in nonnociceptive sensory neurons in this model, we have compared the electrophysiological properties of primary nonnociceptive sensory neurons at ,1 and .2 weeks after CIBP model induction with properties in sham control animals. Methods: Copenhagen rats were injected with 10 6 MAT-LyLu rat prostate cancer cells into the distal femur epiphysis to generate a model of CIBP. After von Frey tactile measurement of mechanical withdrawal thresholds, the animals were prepared for acute electrophysiological recordings of mechanically sensitive neurons in the DRG in vivo. Results: The mechanical withdrawal threshold progressively decreased in CIBP model rats. At ,1 week after model induction, there were no changes observed in nonnociceptive Ab-fiber DRG neurons between CIBP model rats and sham rats. However, at .2 weeks, the Ab-fiber low-threshold mechanoreceptors (LTMs) in CIBP model rats exhibited a slowing of the dynamics of action potential (AP) genesis, including wider AP duration and lower AP amplitude compared with sham rats. Furthermore, enhanced excitability of Ab-fiber LTM neurons was observed as an excitatory discharge in response to intracellular injection of depolarizing current into the soma. Conclusion: After induction of the CIBP model, Ab-fiber LTMs at .2 weeks but not ,1 week had undergone changes in electrophysiological properties. Importantly, changes observed are consistent with observations in models of peripheral neuropathy. Thus, Ab-fiber nonnociceptive primary sensory neurons might be involved in the peripheral sensitization and tumorinduced tactile hypersensitivity in CIBP.
Simultaneous Pressure Waves are an Essential Component of Human Colon Motor Function Assessment, Using High-resolution Manometry
Gastroenterology
Experimental physiology, Sep 3, 2017
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...
Experimental physiology, Mar 30, 2016
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 ...
Haustral boundary contractions in the proximal 3-taeniated rabbit colon
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...
Electrophysiological basis of excitation of canine colonic circular muscle by cholinergic agents and substance P
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...
Electrical coupling and pacemaker activity in colonic smooth muscle
The American journal of physiology, 1988
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...
Potassium channel activation by cromakalim affects the slow wave type action potential of colonic smooth muscle
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...