Electrotonic Coupling between Human Atrial Myocytes and Fibroblasts Alters Myocyte Excitability and Repolarization

Maleckar, Mary M.; Greenstein, Joseph L.; Giles, Wayne R.; Trayanova, Natalia A.

doi:10.1016/j.bpj.2009.07.054

Cited by 122 publications

(163 citation statements)

References 34 publications

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“…For fibroblasts, previous studies using myocytefibroblast co-culture models have shown that the fibroblasts depolarized electrotonically coupled myocytes (Miragoli et al, 2006;MacCannell et al, 2007;Jacquemet and Henriquez, 2008;Maleckar et al, 2009). Our simulations also showed a depolarizing effect of coupled fibroblasts on the resting membrane potential of ventricular myocytes.…”

Section: Effects Of Fibroblast Coupling On Human Ventricular Myocyte supporting

confidence: 70%

“…The main reasons are that: (1) There is lack of experimental data due to the small size of individual fibroblasts ; (2) Ca 2+ current, as a control factor of active tension, has not been identified for membrane ionic currents in fibroblasts Shibukawa et al, 2005;MacCannell et al, 2007;Maleckar et al, 2009). The active force of fibroblasts was therefore ignored at the cellular level in this study.…”

Section: Model Frameworkmentioning

confidence: 99%

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Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study

Zhan

Xia

Shou

et al. 2014

J. Zhejiang Univ. Sci. B

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Abstract:In this study, the effects of cardiac fibroblast proliferation on cardiac electric excitation conduction and mechanical contraction were investigated using a proposed integrated myocardial-fibroblastic electromechanical model. At the cellular level, models of the human ventricular myocyte and fibroblast were modified to incorporate a model of cardiac mechanical contraction and cooperativity mechanisms. Cellular electromechanical coupling was realized with a calcium buffer. At the tissue level, electrical excitation conduction was coupled to an elastic mechanics model in which the finite difference method (FDM) was used to solve electrical excitation equations, and the finite element method (FEM) was used to solve mechanics equations. The electromechanical properties of the proposed integrated model were investigated in one or two dimensions under normal and ischemic pathological conditions. Fibroblast proliferation slowed wave propagation, induced a conduction block, decreased strains in the fibroblast proliferous tissue, and increased dispersions in depolarization, repolarization, and action potential duration (APD). It also distorted the wave-front, leading to the initiation and maintenance of re-entry, and resulted in a sustained contraction in the proliferous areas. This study demonstrated the important role that fibroblast proliferation plays in modulating cardiac electromechanical behaviour and which should be considered in planning future heart-modeling studies.

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Section: Effects Of Fibroblast Coupling On Human Ventricular Myocyte supporting

confidence: 70%

Section: Model Frameworkmentioning

confidence: 99%

Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study

Zhan

Xia

Shou

et al. 2014

J. Zhejiang Univ. Sci. B

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“…Other publications like [4], [8], and [7] have also investigated the influence of myocyte-fibroblast coupling in the human atrium. Here, we consider for the first time the differential effects on a heterogeneous set of cellular models representing different regions within the human atria.…”

Section: Discussionmentioning

confidence: 99%

“…The 10 different regions are the right and left atrial working myocardium (RA and LA), the right and left atrial appendage (RAA and LAA), Bachmann's bundle (BB), the crista terminalis (CT), pulmonary veins (PV), the septum (Sep), and the mitral and tricuspid valve ring (MVR and TVR). Each of these model variants were coupled to the human atrial fibroblast model proposed by Maleckar et al [4]. The fibroblast model of type Active 1 was chosen with a resting membrane voltage of -47.8 mV.…”

Section: Methodsmentioning

confidence: 99%

Effects of Fibroblasts coupling on the Electrophysiology of Cardiomyocytes from Different Regions of the Human Atrium: a Simulation Study

Seemann

Loewe

Wülfers

2017

Computing in Cardiology Conference (CinC)

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Atrial fibrillation is a common cardiac arrhythmia. The disturbance of the normal repolarization process due to heterogeneous myocyte-fibroblast coupling might play a role for this disease. We investigate this interaction in the heterogeneous atrium using a computational approach.Human atrial myocyte computational models representing 10 different regions of the atrium were each coupled to a human atrial fibroblast model and the impact of the myocyte-fibroblast coupling on action potential measures was investigated.Myocytes from the pulmonary vein are affected most by the coupling to fibroblasts. Action potential amplitude is reduced from 105 mV to 94 mV and the upstroke velocity changes from 192 V/s to 152 V/s, potentially reducing the conduction velocity. In general, the action potential duration of myocytes with short action potentials is prolonged and that of those with long is shortened.The large effect on pulmonary vein action potentials is mainly due to reduced I K1 in these cells compared to other regions of the atrium. The strong effects of fibroblast coupling to pulmonary vein myocytes are likely to be an additional reason for the crucial role of the pulmonary veins in atrial fibrillation. IntroductionCardiac arrhythmias are a high burden to the health systems and quality of life. The most common arrhythmia is atrial fibrillation (AF), which affects more than 10% of the population older than 70 and more than 1% of the population in general with an upward trend [1]. The mechanisms of initiation and perpetuation of this arrhythmia are not yet fully understood. Both trigger and substrate changes need to be present in order to allow progression of AF. In this regard, the pulmonary vein (PV) regions play an important role as they are often source of triggered activity. Substrate changes, e.g., by fibroblasts coupling to myocytes, disturb the normal repolarization process. This might play a significant role in the perpetuation of AF.Cardiac myocytes from different regions of the atrium show differences in ion channel density [2]. This manifests in action potential (AP) morphology changes and in action potential duration (APD) variations. This heterogeneity of the AP seems to play an important role for the normal repolarization process leading to an overall more homogeneous repolarization as early activated cells tend to have a longer APD than late activated cells [2]. During progression of AF, the remodeling processes involve the activation of fibroblasts and an increase in fibrosis in addition to electrophysiological remodeling. Up to now, it is not clear if the fibroblasts couple to atrial cardiomyocytes and how they influence the regionally varying APs. Additionally, it is not known if and how myocyte-fibroblast coupling contributes to the perpetuation and progression of atrial fibrillation. This work uses a single cell computational approach to investigates the effects of coupled fibroblasts on atrial cells from different regions of the atrium before electrophysiological remodeling happens. Materi...

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“…Ggap was set to 0.5 nS [1]. Additionally, the number of attached fibroblasts to a single myocyte varied from 0 to [8]. APDs were measured at 90% of repolarization (APD90).…”

Section: Cellular Simulations (0d)mentioning

confidence: 99%

In Silico Analysis of the Effects of Fibroblasts Coupling to Atrial Myocytes under Conditions of Atrial Fibrillation Remodeling

Sánchez

Trénor

Sáiz

2017

Computing in Cardiology Conference (CinC)

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Electrotonic Coupling between Human Atrial Myocytes and Fibroblasts Alters Myocyte Excitability and Repolarization

Cited by 122 publications

References 34 publications

Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study

Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study

Effects of Fibroblasts coupling on the Electrophysiology of Cardiomyocytes from Different Regions of the Human Atrium: a Simulation Study

In Silico Analysis of the Effects of Fibroblasts Coupling to Atrial Myocytes under Conditions of Atrial Fibrillation Remodeling

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