Effects of Na<sup>+</sup>Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization

Zhan, Heqing; Zhang, Jingtao; Lin, Jialun; Han, Guilai

doi:10.1155/2016/6189374

Cited by 4 publications

(7 citation statements)

References 46 publications

(88 reference statements)

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“…Human cardiac fibroblasts (Chatelier et al, 2012;Koivumaki et al, 2014;Li et al, 2009;Zhan et al, 2016) Voltage-gated K + channels Transient outward K + current, I to Delayed rectified K + currents: I K , I Kf Human and rat cardiac fibroblast Rook et al, 1992; Neonatal rat cardiac fibroblasts (Rook et al, 1992;Walsh & Zhang, 2008) Inward-rectifier K + channels K ir , IK v Human lung fibroblasts (Roach et al, 2013) Human cardiac fibroblasts (Aguilar et al, 2014;Li et al, 2009) Canine atrial fibroblasts (Benamer et al, 2009) ATP-activated K + channels K ATP Rat ventricular fibroblasts (Benamer et al, 2009) Human dermal fibroblasts (Bednarczyk et al, 2018) TRP channels TRPA1, TRPC1, TRPC3, TRPC4, TRPC6, TRPV4, TRPM2, TRPM7 Human and mouse lung fibroblasts (Hofmann et al, 2017;Rahaman et al, 2014;Wei et al, 2009;Yonezawa et al, 2016) Mouse proximal tubular cells (Mannaa et al, 2018) Human and rat hepatic stellate cells (Song et al, 2014) Human, rat, and mouse kidney fibroblasts (Saliba et al, 2015) Rat ventricular fibroblasts (Rose et al, 2007) Human, rat, and mouse cardiac fibroblasts (Chen et al, 2010;Du et al, 2010;Li et al, 2019;Mannaa et al, 2018;Oguri et al, 2014;Rahaman et al, 2014;Runnels et al, 2002;Saliba et al, 2015;Song et al, 2014) Cl − channels I Cl-swell , ClC-3, I Cl Human cardiac fibroblasts (Li et al, 2009;…”

Section: Types Of Ion Channels Names Of Ion Channels Cell Types Exprementioning

confidence: 99%

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Roach

Bradding

2020

British J Pharmacology

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The role of Ca2+ signalling in fibroblasts is of great interest in fibrosis‐related diseases. Intracellular free Ca2+ ([Ca2+]i) is a ubiquitous secondary messenger, regulating a number of cellular functions such as secretion, metabolism, differentiation, proliferation and contraction. The intermediate conductance Ca2+‐activated K+ channel KCa3.1 is pivotal in Ca2+ signalling and plays a central role in fibroblast processes including cell activation, migration and proliferation through the regulation of cell membrane potential. Evidence from a number of approaches demonstrates that KCa3.1 plays an important role in the development of many fibrotic diseases, including idiopathic pulmonary, renal tubulointerstitial fibrosis and cardiovascular disease. The KCa3.1 selective blocker senicapoc was well tolerated in clinical trials for sickle cell disease, raising the possibility of rapid translation to the clinic for people suffering from pathological fibrosis. This review after analysing all the data, concludes that targeting KCa3.1 should be a high priority for human fibrotic disease.

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Section: Types Of Ion Channels Names Of Ion Channels Cell Types Exprementioning

confidence: 99%

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Roach

Bradding

2020

British J Pharmacology

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“…In addition, I Na_Mfb is added in the Mfb model. According to our previous work [9], equations of I Na_Mfb is given by…”

Section: Model Of Human Atrial Mfbsmentioning

confidence: 99%

“…In previous study, we have found that the Nav 1.5  subunit, which generates I Na_myofb , regenerated action potentials (APs) in myocytes and Mfbs [9]. In this study, we aimed to investigate the role of Mfbs on the mechanical contraction of cardiac fiber.…”

Section: Introductionmentioning

confidence: 99%

Myofibroblasts Alter Tension and Strain of Cardiac Fiber: A Computational Study

Zhan¹,

Zhang²

2019

2019 Computing in Cardiology Conference (CinC)

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In heart pathological conditions, fibroblasts proliferate and differentiate into myofibroblasts (Mfbs). This study aimed to investigate the role of Mfbs on the mechanical contraction of cardiac fiber. Mathematical modeling was done using a combination of (1) the Maleckar et al. model of the human atrial myocyte, (2) the MacCannell et al. active model of the human cardiac Mfb, (3) our formulation of I Na_myofb based upon experimental findings from Chatelier et al., and (4) the Hill three-element rheological scheme of a single segment of cardiac fiber. For Mfb-myocyte coupling, different ratios of myocytes to Mfbs and gap-junctional conductances were set based on available physiological data. Both isometric contraction and isotonic contraction were considered to illustrate the effect of Mfbs on cardiac fiber's tension and strain. The results showed that (1) Mfbs decreased APD 50 and increased V rest depolarization, (2) Mfbs regulated myocyte peak force and (3) Mfbs reduced the fiber peak force in isometric contraction and the fiber peak strain in isotonic contraction. The identified effects demonstrated that Mfbs play an important role of modulating cardiac mechanical behavior. It should be considered in future pathological cardiac mathematical modeling, such as atrial fibrillation and cardiac fibrosis.

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“…Our previous study has found that I Na_myofb and I MGC_Mfb regenerated APs in myocytes and Mfbs [28]. In this study, we aimed to investigate the role of I SAC , I Na_Mfb , and I MGC_Mfb in the mechanical contraction of cardiac myocyte.…”

Section: Introductionmentioning

confidence: 99%

“…At the cellular level, processes of fibrotic remodeling are represented as fibroblast proliferation and phenotype switching [23, 24]. Simulation results showed that coupling of fibroblasts or Mfbs to atrial myocytes resulted in shorter duration of the action potential (APD), slower conduction, and spiral wave breakups [25–28].…”

Section: Introductionmentioning

confidence: 99%

Stretch-activated current in human atrial myocytes and Na+ current and mechano-gated channels’ current in myofibroblasts alter myocyte mechanical behavior: a computational study

et al. 2019

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BackgroundThe activation of stretch-activated channels (SACs) in cardiac myocytes, which changes the phases of action potential repolarization, is proven to be highly efficient for the conversion of atrial fibrillation. The expression of Na+ current in myofibroblasts (Mfbs) regenerates myocytes’ action potentials, suggesting that Mfbs play an active role in triggering cardiac rhythm disturbances. Moreover, the excitation of mechano-gated channels (MGCs) in Mfbs depolarizes their membrane potential and contributes to the increased risk of post-infarct arrhythmia. Although these electrophysiological mechanisms have been largely known, the roles of these currents in cardiac mechanics are still debated. In this study, we aimed to investigate the mechanical influence of these currents via mathematical modeling. A novel mathematical model was developed by integrating models of human atrial myocyte (including the stretch-activated current, Ca2+–force relation, and mechanical behavior of a single segment) and Mfb (including our formulation of Na+ current and mechano-gated channels’ current). The effects of the changes in basic cycle length, number of coupled Mfbs and intercellular coupling conductance on myocyte mechanical properties were compared.ResultsOur results indicated that these three currents significantly regulated myocyte mechanical parameters. In isosarcometric contraction, these currents increased segment force by 13.8–36.6% and dropped element length by 12.1–31.5%. In isotonic contraction, there are 2.7–5.9% growth and 0.9–24% reduction. Effects of these currents on the extremum of myocyte mechanical parameters become more significant with the increase of basic cycle length, number of coupled Mfbs and intercellular coupling conductance.ConclusionsThe results demonstrated that stretch-activated current in myocytes and Na+ current and mechano-gated channels’ current in Mfbs significantly influenced myocyte mechanical behavior and should be considered in future cardiac mechanical mathematical modeling.

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Effects of Na⁺Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization

Cited by 4 publications

References 46 publications

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Myofibroblasts Alter Tension and Strain of Cardiac Fiber: A Computational Study

Stretch-activated current in human atrial myocytes and Na+ current and mechano-gated channels’ current in myofibroblasts alter myocyte mechanical behavior: a computational study

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Effects of Na+Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization

Cited by 4 publications

References 46 publications

Ca2+ signalling in fibroblasts and the therapeutic potential of KCa3.1 channel blockers in fibrotic diseases

Ca2+ signalling in fibroblasts and the therapeutic potential of KCa3.1 channel blockers in fibrotic diseases

Myofibroblasts Alter Tension and Strain of Cardiac Fiber: A Computational Study

Stretch-activated current in human atrial myocytes and Na+ current and mechano-gated channels’ current in myofibroblasts alter myocyte mechanical behavior: a computational study

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Effects of Na⁺Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases