Transverse tubules are a common feature in large mammalian atrial myocytes including human

Richards, Mark; Clarke, Jessica D.; Saravanan, Palaniappan; Voigt, Niels; Dobrev, Dobromir; Eisner, David; Trafford, Andrew W.; Dibb, Katharine M.

doi:10.1152/ajpheart.00284.2011

Cited by 136 publications

(168 citation statements)

References 46 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…In the present study, mouse left atrial myocytes had a substantial TT density comparable to the values described for larger mammals (e.g., sheep, dog) (12,13). Recent work in human right atrial tissue has shown the presence of TTs, albeit less abundant than in other large mammals (cow, horse, sheep) (33). A denser TT system leads to more DHPR-RyR2 pairs at the junctional SR (jSR), thus facilitating (near-) simultaneous CaT activation throughout the cell (34).…”

Section: Discussionsupporting

confidence: 81%

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Greiser¹,

Kerfant²,

Williams³

et al. 2014

J. Clin. Invest.

104

163

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 81%

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Greiser¹,

Kerfant²,

Williams³

et al. 2014

J. Clin. Invest.

104

163

View full text Add to dashboard Cite

“…T-tubules were recently documented in sheep and human AMs 22 . Current evidence suggests that few T-tubules exist in AM cells and typically in larger mammals like sheep and humans, but not in small rodents 23 .…”

mentioning

confidence: 98%

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles

Wagner

Brandenburg

Kohl

et al. 2014

JoVE

View full text Add to dashboard Cite

In cardiac myocytes a complex network of membrane tubules -the transverse-axial tubule system (TATS) -controls deep intracellular signaling functions. While the outer surface membrane and associated TATS membrane components appear to be continuous, there are substantial differences in lipid and protein content. In ventricular myocytes (VMs), certain TATS components are highly abundant contributing to rectilinear tubule networks and regular branching 3D architectures. It is thought that peripheral TATS components propagate action potentials from the cell surface to thousands of remote intracellular sarcoendoplasmic reticulum (SER) membrane contact domains, thereby activating intracellular Ca 2+ release units (CRUs). In contrast to VMs, the organization and functional role of TATS membranes in atrial myocytes (AMs) is significantly different and much less understood. Taken together, quantitative structural characterization of TATS membrane networks in healthy and diseased myocytes is an essential prerequisite towards better understanding of functional plasticity and pathophysiological reorganization.Here, we present a strategic combination of protocols for direct quantitative analysis of TATS membrane networks in living VMs and AMs. For this, we accompany primary cell isolations of mouse VMs and/or AMs with critical quality control steps and direct membrane staining protocols for fluorescence imaging of TATS membranes. Using an optimized workflow for confocal or superresolution TATS image processing, binarized and skeletonized data are generated for quantitative analysis of the TATS network and its components. Unlike previously published indirect regional aggregate image analysis strategies, our protocols enable direct characterization of specific components and derive complex physiological properties of TATS membrane networks in living myocytes with high throughput and open access software tools. In summary, the combined protocol strategy can be readily applied for quantitative TATS network studies during physiological myocyte adaptation or disease changes, comparison of different cardiac or skeletal muscle cell types, phenotyping of transgenic models, and pharmacological or therapeutic interventions.

show abstract

“…4 Our current understanding of the 3-dimensional (3D) organization of t-ts is mainly derived from studies using confocal microscopy. [5][6][7] Elegant experiments have revealed that the t-ts form regular arrays with a periodicity that correlates to the position of the Z-lines. 8 The dimensions and branching patterns are varied and species-dependent.…”

mentioning

confidence: 99%

Three-Dimensional Reconstruction of Cardiac Sarcoplasmic Reticulum Reveals a Continuous Network Linking Transverse-Tubules

Pinali

Bennett

Davenport

et al. 2013

Circulation Research

120

127

View full text Add to dashboard Cite

T ransverse-tubules (t-ts) are invaginations of the plasma membrane, which in cardiac muscle facilitate transmission of the action potential from the exterior to interior of the cell. Dyads or couplons are formed along regions of the t-ts by the close apposition of the junctional portion of the sarcoplasmic reticulum (jSR). It is within the compartment formed by these 2 structures, the dyadic cleft, that the contractile function in the heart is regulated by the interplay between the L-type voltage-gated Ca 2+ channel (LTCC) localized to the t-ts and the ryanodine receptor (RyR2) anchored in the jSR.1 Critical to this regulation is the arrangement of the jSR and t-t membranes, which are held in a precise geometric organization 2 separated by a gap of 12 to 15 nm. Changes to the microanatomy between the 2 membranes, and hence the spatial relationship between the LTCCs and RyR2s, are associated with Ca 2+ handling abnormalities and impaired contractile function, 3 although the effect on systolic Ca 2+ remains equivocal. 4 Our current understanding of the 3-dimensional (3D) organization of t-ts is mainly derived from studies using confocal microscopy. [5][6][7] Elegant experiments have revealed that the t-ts form regular arrays with a periodicity that correlates to the position of the Z-lines. 8 The dimensions and branching patterns are varied and species-dependent. For example, rat myocytes are shown to have a more geometrically complex arrangement compared with the human t-t system, which has a radial distribution within the cell, akin to the spokes of a wheel. 9 Recently, the development of stimulated emission depletion microscopy has pushed the resolution frontier to ≈60 nm in the focal plane, providing ultrastructural details of the t-t system in control and failing rat hearts showing Rationale: The organization of the transverse-tubular (t-t) system and relationship to the sarcoplasmic reticulum (SR) underpins cardiac excitation-contraction coupling. The architecture of the SR, and relationship with the t-ts, is not well characterized at the whole-cell level. Furthermore, little is known regarding changes to SR ultrastructure in heart failure.Objective: The aim of this study was to unravel interspecies differences and commonalities between the relationship of SR and t-t networks within cardiac myocytes, as well as the modifications that occur in heart failure, using a novel high-resolution 3-dimensional (3D) imaging technique. Methods and Results:Using serial block face imaging coupled with scanning electron microscopy and image analysis, we have generated 3D reconstructions of whole cardiomyocytes from sheep and rat left ventricle, revealing that the SR forms a continuous network linking t-ts throughout the cell in both species. In sheep, but not rat, the SR has an intimate relationship with the sarcolemma forming junctional domains. 3D reconstructions also reveal details of the sheep t-t system. Using a model of tachypacing-induced heart failure, we show that there are populations of swollen and collap...

show abstract

Transverse tubules are a common feature in large mammalian atrial myocytes including human

Cited by 136 publications

References 46 publications

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles

Three-Dimensional Reconstruction of Cardiac Sarcoplasmic Reticulum Reveals a Continuous Network Linking Transverse-Tubules

Contact Info

Product

Resources

About