Modelling the cardiac transverse-axial tubular system

Pásek, Michal; Šimurda, Jiří; Christé, Georges; Orchard, Clive H.

doi:10.1016/j.pbiomolbio.2007.07.021

Cited by 30 publications

(31 citation statements)

References 68 publications

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“…Using published data for Σ = (0.2 ± 0.1) 10 4 ·cm −1 (17,(30)(31)(32) and R m = (3.25 ± 1.15) kΩ·cm 2 (33) and our measured K′ we find λ = 290 ± 90 μm. This value, in line with prior theoretical models (34), is one order of magnitude larger than the cellular radius, indicating a remarkable safety factor of the normal TATS structure in passively conveying membrane potential changes across the cell: A passive conduction-based drop of only ∼4 mV in AP amplitude can be estimated from the surface sarcolemma to the cell core. Although indirect, this is an experimental assessment of the characteristic length constant of the tubular network, having been estimated only theoretically for a long time.…”

Section: Discussionsupporting

confidence: 85%

Quantitative assessment of passive electrical properties of the cardiac T-tubular system by FRAP microscopy

Scardigli

Crocini

Ferrantini

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Well-coordinated activation of all cardiomyocytes must occur on every heartbeat. At the cell level, a complex network of sarcolemmal invaginations, called the transverse-axial tubular system (TATS), propagates membrane potential changes to the cell core, ensuring synchronous and uniform excitation-contraction coupling. Although myocardial conduction of excitation has been widely described, the electrical properties of the TATS remain mostly unknown. Here, we exploit the formal analogy between diffusion and electrical conductivity to link the latter with the diffusional properties of TATS. Fluorescence recovery after photobleaching (FRAP) microscopy is used to probe the diffusion properties of TATS in isolated rat cardiomyocytes: A fluorescent dextran inside TATS lumen is photobleached, and signal recovery by diffusion of unbleached dextran from the extracellular space is monitored. We designed a mathematical model to correlate the time constant of fluorescence recovery with the apparent diffusion coefficient of the fluorescent molecules. Then, apparent diffusion is linked to electrical conductivity and used to evaluate the efficiency of the passive spread of membrane depolarization along TATS. The method is first validated in cells where most TATS elements are acutely detached by osmotic shock and then applied to probe TATS electrical conductivity in failing heart cells. We find that acute and pathological tubular remodeling significantly affect TATS electrical conductivity. This may explain the occurrence of defects in action potential propagation at the level of single T-tubules, recently observed in diseased cardiomyocytes.cardiac disease | transverse-axial tubular system | diffusion | electrical conductivity | porous rock T he sequential and coherent recruitment of all cardiomyocytes that occurs on every heartbeat is fundamental for proper contraction of the heart. Every heartbeat is triggered by a depolarizing event, the action potential (AP), spontaneously generated in cardiac pacemaker cells, which propagates through the conductive tissue and the working myocardium. The well-coordinated activation of all cardiomyocytes involves a spreading AP wave, conducted from cell to cell throughout the lattice of interconnections called gap junctions. The 3D electrical network of cardiomyocytes includes a finer order of complexity that involves a system of deep sarcolemmal membrane invaginations within each cell. As a network within a network, these sarcolemmal invaginations occur transversely with a periodicity roughly corresponding to that of sarcomere z-lines (transverse tubules, or T-tubules) and branch in the longitudinal direction (axial tubules) to form a complex system in atrial and ventricular cells, named the transverse-axial tubular system (TATS) (1, 2). The TATS allows membrane potential changes to propagate rapidly into the cardiomyocyte core and is considered an ultimate structural player for excitation-contraction coupling. During rapid depolarization, such as seen during the AP, Ca 2+ enters the cytos...

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Section: Discussionsupporting

confidence: 85%

Quantitative assessment of passive electrical properties of the cardiac T-tubular system by FRAP microscopy

Scardigli

Crocini

Ferrantini

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The model geometry was derived from the published structural data [9], [11], [23]. The cell model contains one repeating unit inside the ventricular myocyte, including single t-tubule and its surrounding half-sarcomeres (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…The volume of the model compartment was estimated to be ~27.68 μm 3 . The compartment membrane area was ~9.34μm 2 where the percentage of cell membrane within t-tubule was 58% (~5.42 μm 2 ) and within the surface membrane 42% (~3.92 μm 2 ), [9], [11], [23], [25]. …”

Section: Methodsmentioning

confidence: 99%

“…Recently it has been also emphasized that biophysically realistic computational models, incorporating transverse-axial t-tubular system and considering geometric irregularities and inhomogeneities in the distribution of ion-transporting proteins, are missing and needed [11], [23]. For this reason, our main goal here was to develop a detailed 3-D model at the sub-cellular level that would allow us to examine how the distribution of Ca 2+ fluxes via t-tubule and surface membrane may affect Ca 2+ -entry, diffusion and buffering.…”

Section: Introductionmentioning

confidence: 99%

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Multiscale modeling in rodent ventricular myocytes

Michailova

Saucerman

et al. 2009

IEEE Eng. Med. Biol. Mag.

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“…The transverse tubules comprise ∼60% of the total cell membrane area [57]. Ca 2+ transport as in the model illustrated in Fig.…”

Section: Function Of Normal Myocardiummentioning

confidence: 99%

Electromechanical coupling in the cardiac myocyte; stretch-arrhythmia feedback

Keurs

2011

Pflugers Arch - Eur J Physiol

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The macroscopic hallmarks of the normal heartbeat are rapid onset of contraction and rapid relaxation and an inotropic response to both increased end diastolic volume and increased heart rate. At the microscopic level, the calcium ion (Ca(2+)) plays a crucial role in normal cardiac contraction. This paper reviews the cycle of Ca(2+) fluxes during the normal heartbeat, which underlie the coupling between excitation and contraction (ECC) and permit a highly synchronized action of cardiac sarcomeres. Length dependence of the response of the regulatory sarcomeric proteins mediates the Frank-Starling Law of the heart. However, Ca(2+) transport may go astray in heart disease and both jeopardize the exquisite mechanism of systole and diastole and triggering arrhythmias. The interplay between weakened and strong segments in nonuniform cardiac muscle may further lead to mechanoelectric feedback-or reverse excitation contraction coupling (RECC) mediating an early diastolic Ca(2+) transient caused by the rapid force decrease during the relaxation phase. These rapid force changes in nonuniform muscle may cause arrhythmogenic Ca(2+) waves to propagate by activation of neighbouring SR by diffusing Ca(2+) ions.

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Modelling the cardiac transverse-axial tubular system

Cited by 30 publications

References 68 publications

Quantitative assessment of passive electrical properties of the cardiac T-tubular system by FRAP microscopy

Quantitative assessment of passive electrical properties of the cardiac T-tubular system by FRAP microscopy

Multiscale modeling in rodent ventricular myocytes

Electromechanical coupling in the cardiac myocyte; stretch-arrhythmia feedback

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