A Quantitative Model of Human Jejunal Smooth Muscle Cell Electrophysiology

Poh, Yong Cheng; Corrias, Alberto; Cheng, Nicholas; Buist, Martin L.

doi:10.1371/journal.pone.0042385

Cited by 23 publications

(32 citation statements)

References 54 publications

(68 reference statements)

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“…2c). 29 An attempt has also recently been made to mathematically evaluate the electromechanical relationship between slow waves and motility in a cell model by Gajendiran et al , which consisted of a bimodular component, and is dependent on intracellular Ca 2+ concentration (Fig. 2d).…”

Section: Cellular Levelmentioning

confidence: 99%

“…Future modeling studies could incorporate these elements in order to develop mechanistic insights into gastric dysrhythmias. Modeling studies can also incorporate detailed channelopathy models at the cellular level under the multi-scale modeling framework, 29 and offer an opportunity to coordinate the electromechanical coupling activity in the GI tissue.…”

Section: Computational Techniquesmentioning

confidence: 99%

“…13, 28 (c) An intestinal SMC model developed by Poh et al . 29 (d) A gastric electromechanical model developed by Gajendiran et al . 30 showing the relationship between intracellular Ca 2+ (solid line) and normalized force generation (dashed line)in a SMC.…”

Section: Figmentioning

confidence: 99%

“…21 More recently, a SMC model was published by Poh et al containing seven types of ion conductance, reproducing human jejunal smooth muscle cell (hJSMC) slow wave activity (Figure 2(c)). 22 An attempt has also recently been made to mathematically evaluate the electromechanical relationship between slow waves and motility in a cell model by Gajendiran et al, which consisted of a bimodular component, and is dependent on intracellular Ca 2+ concentration (Figure 2(d)). 23 The model simulated the interaction between Ca 2+ and calmodulin which activates myosin light-chain kinase (MLCK) in the first module.…”

Section: Gastrointestinal Smc Modelsmentioning

confidence: 99%

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Toward the virtual stomach: progress in multiscale modeling of gastric electrophysiology and motility

O’Grady

Gao

et al. 2013

WIREs Mechanisms of Disease

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Experimental progress in investigating normal and disordered gastric motility is increasingly being complimented by sophisticated multi-scale modeling studies. Mathematical modeling has become a valuable tool in this effort, as there is an ever-increasing need to gain an integrative and quantitative understanding of how physiological mechanisms achieve coordinated functions across multiple biophysical scales. These interdisciplinary efforts have been particularly notable in the area of gastric electrophysiology, where they are beginning to yield a comprehensive and integrated in-silico organ modeling framework, or ‘virtual stomach’. At the cellular level, a number of biophysically-based mathematical cell models have been developed, and these are now being applied in areas including investigations of gastric electrical pacemaker mechanisms, smooth muscle electrophysiology, and electromechanical coupling. At the tissue level, micro-structural models are being creatively developed and employed to investigate clinically significant questions, such as the functional effects of ICC degradation on gastrointestinal electrical activation. At the organ level, high-resolution electrical mapping and modeling studies are combining to provide improved insights into normal and dysrhythmic gastric electrical activation. These efforts are also enabling detailed forward and inverse modeling studies at the ‘whole body’ level, with implications for diagnostic techniques for gastric dysrhythmias. These recent advances, together with several others highlighted in this review, collectively demonstrate a powerful trend toward applying mathematical models to effectively investigate structure-function relationships and overcome multi-scale challenges in basic and clinical gastrointestinal research.

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Section: Cellular Levelmentioning

confidence: 99%

Section: Computational Techniquesmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Gastrointestinal Smc Modelsmentioning

confidence: 99%

See 2 more Smart Citations

Toward the virtual stomach: progress in multiscale modeling of gastric electrophysiology and motility

O’Grady

Gao

et al. 2013

WIREs Mechanisms of Disease

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“…Such models have furnished a wealth of insight into the fundamental mechanisms underlying electrical excitability. So far, models for a few smooth muscle cell types, incorporating ionic channels and calcium dynamics, have been developed, such as for intestinal [ 26 ], uterine [ 27 , 28 , 29 ], jejunal [ 30 ], gastric [ 31 , 32 ], mesenteric [ 33 ], small bowel [ 34 ] and arterial [ 35 , 36 ] smooth muscle cells.…”

Section: Introductionmentioning

confidence: 99%

A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle

2018

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Urinary incontinence is associated with enhanced spontaneous phasic contractions of the detrusor smooth muscle (DSM). Although a complete understanding of the etiology of these spontaneous contractions is not yet established, it is suggested that the spontaneously evoked action potentials (sAPs) in DSM cells initiate and modulate the contractions. In order to further our understanding of the ionic mechanisms underlying sAP generation, we present here a biophysically detailed computational model of a single DSM cell. First, we constructed mathematical models for nine ion channels found in DSM cells based on published experimental data: two voltage gated Ca2+ ion channels, an hyperpolarization-activated ion channel, two voltage-gated K+ ion channels, three Ca2+-activated K+ ion channels and a non-specific background leak ion channel. The ion channels’ kinetics were characterized in terms of maximal conductances and differential equations based on voltage or calcium-dependent activation and inactivation. All ion channel models were validated by comparing the simulated currents and current-voltage relations with those reported in experimental work. Incorporating these channels, our DSM model is capable of reproducing experimentally recorded spike-type sAPs of varying configurations, ranging from sAPs displaying after-hyperpolarizations to sAPs displaying after-depolarizations. The contributions of the principal ion channels to spike generation and configuration were also investigated as a means of mimicking the effects of selected pharmacological agents on DSM cell excitability. Additionally, the features of propagation of an AP along a length of electrically continuous smooth muscle tissue were investigated. To date, a biophysically detailed computational model does not exist for DSM cells. Our model, constrained heavily by physiological data, provides a powerful tool to investigate the ionic mechanisms underlying the genesis of DSM electrical activity, which can further shed light on certain aspects of urinary bladder function and dysfunction.

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The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications

Paskaranandavadivel

Angeli

et al. 2015

WIREs Mechanisms of Disease

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The intestine comprises a long hollow muscular tube organized in anatomically and functionally discrete compartments, which digest and absorb nutrients and water from ingested food. The intestine also plays key roles in the elimination of waste and protection from infection. Critical to all of these functions is the intricate, highly-coordinated motion of the intestinal tract, known as motility, which is co-regulated by hormonal, neural, electrophysiological and other factors. The Virtual Intestine encapsulates a series of mathematical models of intestinal function in health and disease, with a current focus on motility, and particularly electrophysiology. The Virtual Intestine is being cohesively established across multiple physiological scales, from sub/cellular functions to whole organ levels, facilitating quantitative evaluations that present an integrative in-silico framework. The models are also now finding broad physiological applications, including in evaluating hypotheses of slow wave pacemaker mechanisms, smooth muscle electrophysiology, structure-function relationships, and electromechanical coupling. Clinical applications are also beginning to follow, including in the pathophysiology of motility disorders, diagnosing intestinal ischemia, and visualizing colonic dysfunction. These advances illustrate the emerging potential of the Virtual Intestine to effectively address multi-scale research challenges in interdisciplinary gastrointestinal sciences.

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A Quantitative Model of Human Jejunal Smooth Muscle Cell Electrophysiology

Cited by 23 publications

References 54 publications

Toward the virtual stomach: progress in multiscale modeling of gastric electrophysiology and motility

Toward the virtual stomach: progress in multiscale modeling of gastric electrophysiology and motility

A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle

The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications

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