T-tubule formation in cardiacmyocytes: two possible mechanisms?

Maio, Alessandro Di; Karko, Kimberly L.; Snopko, Rose M.; Mejía-Alvarez, Rafael; Franzini‐Armstrong, Clara

doi:10.1007/s10974-007-9121-x

Cited by 55 publications

(40 citation statements)

References 33 publications

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“…One commonly occurring feature is a crescent or doughnut shaped cluster. In some cases such shapes would be consistent with the presence of a t-tubule opening (Ϸ200 nm) and RyR clusters at the mouth of t-tubules have been seen previously in EM thin sections (25).…”

Section: Ryr Clusters Have Complex Geometriessupporting

confidence: 88%

Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes

Baddeley

Jayasinghe

Lam

et al. 2009

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

264

347

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We have applied an optical super-resolution technique based on single-molecule localization to examine the peripheral distribution of a cardiac signaling protein, the ryanodine receptor (RyR), in rat ventricular myocytes. RyRs form clusters with a mean size of approximately 14 RyRs per cluster, which is almost an order of magnitude smaller than previously estimated. Clusters were typically not circular (as previously assumed) but elongated with an average aspect ratio of 1.9. Edge-to-edge distances between adjacent RyR clusters were often <50 nm, suggesting that peripheral RyR clusters may exhibit strong intercluster signaling. The wide variation of cluster size, which follows a near-exponential distribution, is compatible with a stochastic cluster assembly process. We suggest that calcium sparks may be the result of the concerted activation of several RyR clusters forming a functional ''supercluster'' whose gating is controlled by both cytosolic and sarcoplasmic reticulum luminal calcium levels.excitation-contraction coupling ͉ fluorescence ͉ heart ͉ single molecule ͉ super-resolution

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Section: Ryr Clusters Have Complex Geometriessupporting

confidence: 88%

Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes

Baddeley

Jayasinghe

Lam

et al. 2009

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

264

347

View full text Add to dashboard Cite

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“…In mammal cardiomyocytes, peripheral couplons (the junction between the surface of the cell membrane and the SR) already exist during embryogenesis [14,15]. However, the morphogenesis of TTs and the formation of TT-SR couplons begin at a relatively late stage [14,16].…”

mentioning

confidence: 99%

“…However, the morphogenesis of TTs and the formation of TT-SR couplons begin at a relatively late stage [14,16]. The TT network does not appear until 7-10 days after birth [14,17].…”

mentioning

confidence: 99%

“…However, the morphogenesis of TTs and the formation of TT-SR couplons begin at a relatively late stage [14,16]. The TT network does not appear until 7-10 days after birth [14,17]. Two possible models for TT development, the invagination model and the pre-association model, have been proposed [14,17].…”

mentioning

confidence: 99%

“…The TT network does not appear until 7-10 days after birth [14,17]. Two possible models for TT development, the invagination model and the pre-association model, have been proposed [14,17]. In the invagination model, TTs originate from the surface membrane and subsequently extend into the center of the cell [14,17].…”

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confidence: 99%

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Morphogenesis of T-tubules in heart cells: the role of junctophilin-2

Han

Wang

et al. 2013

Sci. China Life Sci.

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The T-tubule (TT) system forms the structural basis for excitation-contraction coupling in heart and muscle cells. The morphogenesis of the TT system is a key step in the maturation of heart cells because it does not exist in neonatal cardiomyocytes. In the present study, we quantified the morphological changes in TTs during heart cell maturation and investigated the role of junctophilin-2 (JP2), a protein known to anchor the sarcoplasmic reticulum (SR) to TT, in changes to TT morphological parameters. Analysis of confocal images showed that the transverse elements of TTs increased, while longitudinal elements decreased during the maturation of TTs. Fourier transform analysis showed that the power of ~2 m spatial components increased with cardiomyocytes maturation. These changes were preceded by increased expression of JP2, and were reversed by JP2 knockdown. These findings indicate that JP2 is required for the morphogenesis of TTs during heart development.

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Using hiPSC‐CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia

Arslanova

Shafaattalab

et al. 2021

Current Protocols

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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac arrhythmia condition, triggered by physical or acute emotional stress, that predominantly expresses early in life. Gain‐of‐function mutations in the cardiac ryanodine receptor gene (RYR2) account for the majority of CPVT cases, causing substantial disruption of intracellular calcium (Ca2+) homeostasis particularly during the periods of β‐adrenergic receptor stimulation. However, the highly variable penetrance, patient outcomes, and drug responses observed in clinical practice remain unexplained, even for patients with well‐established founder RyR2 mutations. Therefore, investigation of the electrophysiological consequences of CPVT‐causing RyR2 mutations is crucial to better understand the pathophysiology of the disease. The development of strategies for reprogramming human somatic cells to human induced pluripotent stem cells (hiPSCs) has provided a unique opportunity to study inherited arrhythmias, due to the ability of hiPSCs to differentiate down a cardiac lineage. Employment of genome editing enables generation of disease‐specific cell lines from healthy and diseased patient‐derived hiPSCs, which subsequently can be differentiated into cardiomyocytes. This paper describes the means for establishing an hiPSC‐based model of CPVT in order to recapitulate the disease phenotype in vitro and investigate underlying pathophysiological mechanisms. The framework of this approach has the potential to contribute to disease modeling and personalized medicine using hiPSC‐derived cardiomyocytes. © 2021 Wiley Periodicals LLC.

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T-tubule formation in cardiacmyocytes: two possible mechanisms?

Cited by 55 publications

References 33 publications

Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes

Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes

Morphogenesis of T-tubules in heart cells: the role of junctophilin-2

Using hiPSC‐CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia

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