Evidence of intercellular coupling between co‐cultured adult rabbit ventricular myocytes and myofibroblasts

Chilton, Lisa; Giles, Wayne R.; Smith, Godfrey L.

doi:10.1113/jphysiol.2007.135038

Cited by 131 publications

(121 citation statements)

References 36 publications

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“…4,35,37,38 In this setting, fibroblasts undergo a phenotype shift to smooth muscle actin-positive myofibroblasts that exhibit gap junction coupling among themselves and with cardiomyocytes. 37,38 Myofibroblast density-dependent reductions in cardiomyocyte resting membrane potential, CV slowing (≤35%), 37 and successful propagation across fibroblast barriers ≤300 µm by guest on May 12, 2018 http://circres.ahajournals.org/ Downloaded from wide 4 were observed in patterned neonatal rat ventricular myocytes coated with cardiac myofibroblasts. Results from these coculture studies should be treated with some circumspection; because there are structural and functional differences between neonatal rat myocytes and adult cardiomyocytes, 28 myofibroblast electrophysiology was not characterized, and gap junction coupling differs from that observed in adult ventricular myofibroblast myocyte cocultures.…”

Section: Impulse Transmission Between Myocytesmentioning

confidence: 99%

“…39 Measured resting membrane potentials for fibroblasts and myofibroblasts are significantly less negative than associated cardiomyocytes. 4,35,38,39 Computer models based on these electrophysiological data have been used to investigate potential effects of electrotonic coupling between cardiomyocytes and fibroblasts. 40,41 More recently, this approach has been extended to include interactions among myofibroblasts and cardiomyocytes.…”

Section: Impulse Transmission Between Myocytesmentioning

confidence: 99%

“…4,35 This has been driven by demonstrations of bidirectional coupling among myocytes, fibroblasts, and myofibroblasts via functional gap junctions. [36][37][38] A range of membrane ion channels, transporters, and pumps has been identified in cardiac fibroblasts and myofibroblasts. 35 In particular, membrane ion channels that carry inwardly rectifying K + currents and various voltage-dependent outward K + currents have been characterized in adult rat ventricular fibroblasts and myofibroblasts.…”

Section: Impulse Transmission Between Myocytesmentioning

confidence: 99%

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Three-Dimensional Impulse Propagation in Myocardium

Smaill

Zhao

Trew

2013

Circulation Research

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I mpulse propagation in the heart depends on the excitability of individual cardiomyocytes, impulse transmission between adjacent myocytes, and the 3-dimensional (3D) arrangement of those cells. These factors operate across a wide range of spatial scales, and normal function at each level ensures that electric activation spreads across the cardiac chambers in a stable rhythm, which triggers efficient contraction. Perturbation of this function can give rise to rhythm disturbance and reentrant activation. The conditions necessary for reentrant arrhythmia have been known in a general sense Abstract: Impulse propagation in the heart depends on the excitability of individual cardiomyocytes, impulse transmission between adjacent myocytes, and the 3-dimensional arrangement of those cells. Here, we review the role of each of these factors in normal and aberrant cardiac electric activation, with particular emphasis on the effects of 3-dimensional myocyte architecture at the tissue scale. The analysis draws on findings from in vivo and in vitro experiments, as well as biophysically based computer models that have been used to integrate and interpret these experimental data. It indicates that discontinuous arrangement of myocytes and extracellular connective tissue at the tissue scale can give rise to current source-to-sink mismatch, spatiotemporal distribution of refractoriness, and rate-sensitive electric instability, which contribute to the initiation and maintenance of reentrant cardiac arrhythmia. This exacerbates the risk of rhythm disturbance associated with heart disease. We conclude that structure-based, multiscale computer models that incorporate accurate information about local cellular electric activity provide a powerful platform for investigating the basis of reentrant cardiac arrhythmia. However, it is important that these models capture key features of structure and related electric function at the tissue scale. (Circ Res. 2013;112:834-848.)Key Words: electric anisotropy ■ electrophysiology ■ fibrosis ■ infarct border zone ■ myocardial architecture ■ normal activation ■ reentrant arrhythmia

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Section: Impulse Transmission Between Myocytesmentioning

confidence: 99%

Section: Impulse Transmission Between Myocytesmentioning

confidence: 99%

Section: Impulse Transmission Between Myocytesmentioning

confidence: 99%

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Three-Dimensional Impulse Propagation in Myocardium

Smaill

Zhao

Trew

2013

Circulation Research

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“…Progressive fibrotic change is a recognised feature of cardiac ageing in both animal32, 33 and human studies 34. Fibrotic change could directly disrupt gap junction function, increasing tissue resistance,35 or increase fibroblast‐cardiomyocyte coupling, increasing effective membrane capacitance 36. More recent studies indeed implicate abnormal gap junction function in both SAN and AVN disease 37, 38.…”

Section: Discussionmentioning

confidence: 99%

Age‐dependent electrocardiographic changes in Pgc‐1β deficient murine hearts

Ahmad

Valli

Salvage

et al. 2017

Clin Exp Pharma Physio

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SummaryIncreasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc‐1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis have not been previously studied. Young (12‐16 weeks) and aged (>52 weeks), wild type (WT) (n = 5 and 8) and Pgc‐1β−/− (n = 9 and 6), mice were anaesthetised and used for electrocardiographic (ECG) recordings. Time intervals separating successive ECG deflections were analysed for differences between groups before and after β1‐adrenergic (intraperitoneal dobutamine 3 mg/kg) challenge. Heart rates before dobutamine challenge were indistinguishable between groups. The Pgc‐1β−/− genotype however displayed compromised nodal function in response to adrenergic challenge. This manifested as an impaired heart rate response suggesting a functional defect at the level of the sino‐atrial node, and a negative dromotropic response suggesting an atrioventricular conduction defect. Incidences of the latter were most pronounced in the aged Pgc‐1β−/− mice. Moreover, Pgc‐1β−/− mice displayed electrocardiographic features consistent with the existence of a pro‐arrhythmic substrate. Firstly, ventricular activation was prolonged in these mice consistent with slowed action potential conduction and is reported here for the first time. Additionally, Pgc‐1β−/− mice had shorter repolarisation intervals. These were likely attributable to altered K+ conductance properties, ultimately resulting in a shortened QTc interval, which is also known to be associated with increased arrhythmic risk. ECG analysis thus yielded electrophysiological findings bearing on potential arrhythmogenicity in intact Pgc‐1β−/− systems in widespread cardiac regions.

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“…Cardiac fibroblasts, which are inexcitable cells, often multiply and connect with cardiac myocytes during fibrosis [9][10][11], a process of cardiac-tissue healing after a myocardial infarction. Fibroblasts in cell culture and in intact tissue can couple with myocytes by expressing either the connexins-43 (Cx43) or Cx45 [12][13][14][15][16]. Zlochiver, et al [15] have shown the expression of Cx43 between fibroblasts and myocytes in a monolayer of myocytes and fibroblasts of neonatal rats; Miragoli, et al [16] have reported that Cx43 and Cx45 are expressed among fibroblasts and between fibroblasts and myocytes in cultured fibroblasts coated over rat-ventricular-myocyte strands.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Fibroblasts on Wave Dynamics in a Mathematical Model for Human Ventricular Tissue

Nayak¹,

Pandit²

2016

Biomat 2015

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We present systematic numerical studies of electrical-wave propagation in two-dimensional (2D) and three-dimensional (3D) mathematical models, for human, ventricular tissue with myocyte cells that are attached (a) regularly and (b) randomly to distributed fibroblasts. In both these cases we show that there is a parameter regime in which single rotating spiral-and scroll-wave states (RS) retain their integrity and do not evolve to a state ST that displays spatiotemporal chaos and turbulence. However, in another range of parameters, we observe a transition from ST to RS states in both 2D or 3D domains and for both cases (a) and (b). Our studies show that the ST-RS transition and rotation period of a spiral or scroll wave in the RS state depends on (i) the coupling strength between myocytes and fibroblasts and (ii) the number of fibroblasts attached to myocytes. We conclude that myocyte-fibroblast coupling strength and the number of fibroblasts are more important for the ST-RS transition than the precise way in which fibroblasts are distributed over myocyte tissue.

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Evidence of intercellular coupling between co‐cultured adult rabbit ventricular myocytes and myofibroblasts

Cited by 131 publications

References 36 publications

Three-Dimensional Impulse Propagation in Myocardium

Three-Dimensional Impulse Propagation in Myocardium

Age‐dependent electrocardiographic changes in Pgc‐1β deficient murine hearts

The Effects of Fibroblasts on Wave Dynamics in a Mathematical Model for Human Ventricular Tissue

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