The role of mammalian cardiac t‐tubules in excitation–contraction coupling: experimental and computational approaches

Orchard, Clive H.; Pásek, Michal; Brette, Fabien

doi:10.1113/expphysiol.2008.043984

Cited by 58 publications

(50 citation statements)

References 75 publications

(144 reference statements)

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“…exchangers seem to have preferential access to Ca 2? released from the SR (Trafford et al 1995 (Eisner et al 1998) and has been suggested to occur predominantly at the t-tubules (Orchard et al 2009) may contribute to Ca 2? homeostasis in the t-tubule lumen.…”

Section: The Modelmentioning

confidence: 97%

“…exchange and sarcolemmal Ca 2? ATPase, occur at the t-tubules (reviewed by Orchard et al 2009;Chase and Orchard 2011). These ion fluxes occur into and out of a space-the t-tubule lumen-which has restricted diffusional access to the bulk extracellular space, a condition that will be exacerbated in the intact tissue in which diffusion will be restricted further by the limited volume of the inter-cellular clefts.…”

Section: Introductionmentioning

confidence: 98%

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Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular Ca2+ in a model of the rat cardiac ventricular myocyte

2012

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The t-tubules of mammalian ventricular myocytes are invaginations of the surface membrane that form a complex network within the cell, with restricted diffusion to the bulk extracellular space. The trans-sarcolemmal flux of many ions, including Ca(2+), occurs predominantly across the t-tubule membrane and thus into and out of this restricted diffusion space. It seems possible, therefore, that ion concentration changes may occur in the t-tubule lumen, which would alter ion flux across the t-tubule membrane. We have used a computer model of the ventricular myocyte, incorporating a t-tubule compartment and experimentally determined values for diffusion between the t-tubule lumen and bulk extracellular space, and ion fluxes across the t-tubule membrane, to investigate this possibility. The results show that influx and efflux of different ion species across the t-tubule membrane are similar, but not equal. Changes of ion concentration can therefore occur close to the t-tubular membrane, thereby altering trans-sarcolemmal ion flux and thus cell function, although such changes are reduced by diffusion to the bulk extracellular space. Slowing diffusion results in larger changes in luminal ion concentrations. These results provide a deeper understanding of the role of the t-tubules in normal cell function, and are a basis for understanding the changes that occur in heart failure as a result of changes in t-tubule structure and ion fluxes.

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Section: The Modelmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular Ca2+ in a model of the rat cardiac ventricular myocyte

2012

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“…This is in keeping with the spatial organization of the mitochondrial network, where polarized mitochondria are usually distributed in rows along the longitudinal axis and very rarely along the transverse axis (with some deviation from this generalization for mitochondria located adjacent to the nuclei of the cell). This could be related to diffusional restrictions imposed by the spatial arrangement of the myofilaments that separate the mitochondria in the transverse direction (14).…”

Section: Longitudinal Vs Transverse Correlation Of Mitochondrial Memmentioning

confidence: 99%

Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters

Kurz

Aon

O’Rourke

et al. 2010

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

123

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Mitochondrial networks in cardiac myocytes under oxidative stress show collective (cluster) behavior through synchronization of their inner membrane potentials (ΔΨ m ). However, it is unclear whether the oscillation frequency and coupling strength between individual mitochondria affect the size of the cluster and vice versa. We used the wavelet transform and developed advanced signal processing tools that allowed us to capture individual mitochondrial ΔΨ m oscillations in cardiac myocytes and examine their dynamic spatio-temporal properties. Heterogeneous frequency behavior prompted us to sort mitochondria according to their frequencies. Signal analysis of the mitochondrial network showed an inverse relationship between cluster size and cluster frequency as well as between cluster amplitude and cluster size. High cross-correlation coefficients between neighboring mitochondria clustered longitudinally along the myocyte striations, indicated anisotropic communication between mitochondria. Isochronal mapping of the onset of myocyte-wide ΔΨ m depolarization further exemplified heterogeneous ΔΨ m among mitochondria. Taken together, the results suggest that frequency and amplitude modulation of clusters of synchronized mitochondria arises by means of strong changes in local coupling between neighboring mitochondria.wavelets | frequency | amplitude | mitochondrial oscillator | mitochondrial coupling M itochondria in cardiac myocytes under the influence of substrate deprivation or oxidative stress have a fundamental role as determinants of cell life or death, with implications that scale to affect the function of the whole heart (1, 2). Cardiac mitochondria are organized in a highly ordered network consisting of intermyofibrillar, subcarcolemmal, and perinuclear (3) mitochondria whose coordinated function controls the energy metabolism of the myocyte (4).In cardiac myocytes, the localized perturbation of a few mitochondria within the overall mitochondrial network can trigger the transition from the physiological to the pathophysiological state by producing synchronized whole-myocyte oscillations of ΔΨ m that can be monitored with the fluorescent dye tetramethylrhodamine ethyl ester (TMRE) (5). The imbalance between reactive oxygen species (ROS) generation and ROS scavenging capacity in a significant proportion of the network (∼60%) (5) is thought to destabilize ΔΨ m beyond a critical point into a state of ROS-induced ROS release. Increased ROS overflow exceeding a threshold level results in the appearance of a spanning cluster of mitochondria oscillating in apparent synchrony throughout the cell as the mitochondrial network locks into a low-frequency, high-amplitude oscillatory mode (6, 7).In many disparate examples of physically and chemically coupled oscillators, synchronization of the system generally arises from an initial nucleus of (spontaneously) synchronized oscillators that integrate neighboring oscillators, thereby increasing the size and signal amplitude of the initial oscillatory nucleus (8-11).When the clus...

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“…The typical structure of adult CMs is characterized by bundles of parallel myofilaments, sarcomeres with Z-disc, A-, I-, and H-band as well as the M-line, which are the structural basis of cardiac muscle contraction. Moreover, the transverse tubules (t-tubules), which emerge into deep invaginations of the plasma membrane of CMs and are rich in ion channels, are crucial for excitation-contraction coupling (ECC) of CMs [5]. Therefore, the mature structure of sarcomeres and t-tubules in ES cell-derived CMs (ES-CMs) are prerequisite for their function and integration in the host tissue after transplantation [6].…”

Section: Introductionmentioning

confidence: 99%

Puerarin Facilitates T-Tubule Development of Murine Embryonic Stem Cell-Derived Cardiomyocytes

Wang

Cui

Tang

et al. 2014

Cell Physiol Biochem

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Aims: The embryonic stem cell-derived cardiomyocytes (ES-CM) is one of the promising cell sources for repopulation of damaged myocardium. However, ES-CMs present immature structure, which impairs their integration with host tissue and functional regeneration. This study used murine ES-CMs as an in vitro model of cardiomyogenesis to elucidate the effect of puerarin, the main compound found in the traditional Chinese medicine the herb Radix puerariae, on t-tubule development of murine ES-CMs. Methods: Electron microscope was employed to examine the ultrastructure. The investigation of transverse-tubules (t-tubules) was performed by Di-8-ANEPPS staining. Quantitative real-time PCR was utilized to study the transcript level of genes related to t-tubule development. Results: We found that long-term application of puerarin throughout cardiac differentiation improved myofibril array and sarcomeres formation, and significantly facilitated t-tubules development of ES-CMs. The transcript levels of caveolin-3, amphiphysin-2 and junctophinlin-2, which are crucial for the formation and development of t-tubules, were significantly upregulated by puerarin treatment. Furthermore, puerarin repressed the expression of miR-22, which targets to caveolin-3. Conclusion: Our data showed that puerarin facilitates t-tubule development of murine ES-CMs. This might be related to the repression of miR-22 by puerarin and upregulation of Cav3, Bin1 and JP2 transcripts.

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The role of mammalian cardiac t‐tubules in excitation–contraction coupling: experimental and computational approaches

Cited by 58 publications

References 75 publications

Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular Ca2+ in a model of the rat cardiac ventricular myocyte

Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular Ca2+ in a model of the rat cardiac ventricular myocyte

Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters

Puerarin Facilitates T-Tubule Development of Murine Embryonic Stem Cell-Derived Cardiomyocytes

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