Transthyretin deposition alters cardiomyocyte sarcomeric architecture, calcium transients, and contractile force

Dittloff, Kyle; Spanghero, Emanuele; Solis-Ocampo, Christopher; Banach, Kathrin; Russell, Brenda

doi:10.14814/phy2.15207

Cited by 4 publications

(2 citation statements)

References 59 publications

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“…As such, α-actinin and CapZ results in this neonatal cardiomyocyte culture will mostly be relevant to the adult rodent. In this work, NRVMs are cultured at a high cell density where they beat spontaneously and form a syncytium with connexons as demonstrated by the free diffusion of calcein AM from one cell to another [ 26 ]. The myriad of differences between 2D cultured NRVMs and the adult heart denote that the biophysical models here are not necessarily applicable to the adult cells within the cardiac tissue in terms of physiologic and pathologic processes.…”

Section: Discussionmentioning

confidence: 99%

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Cardiomyocyte external mechanical unloading activates modifications of α‐actinin differently from sarcomere‐originated unloading

et al. 2023

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Loss of myocardial mass in a neonatal rat cardiomyocyte culture is studied to determine whether there is a distinguishable cellular response based on the origin of mechano‐signals. The approach herein compares the sarcomeric assembly and disassembly processes in heart cells by imposing mechano‐signals at the interface with the extracellular matrix (extrinsic) and at the level of the myofilaments (intrinsic). Experiments compared the effects of imposed internal (inside/out) and external (outside/in) loading and unloading on modifications in neonatal rat cardiomyocytes. Unloading of the cellular substrate by myosin inhibition (1μM mavacamten), or cessation of cyclic strain (1 Hz, 10% strain) after preconditioning, led to significant disassembly of sarcomeric α‐actinin by 6 hrs. In myosin inhibition, this was accompanied by redistribution of intracellular poly‐ubiquitin K48 to the cellular periphery relative to the poly‐ubiquitin K48 reservoir at the I‐band. Moreover, loading and unloading of the cellular substrate led to a three‐fold increase in post translational modifications (PTMs) when compared to the myosin‐specific activation or inhibition. Specifically, phosphorylation increased with loading while ubiquitination increased with unloading, which may involve ERK1/2 and FAK activation. The identified PTMs, including ubiquitination, acetylation, and phosphorylation, are proposed to modify internal domains in α‐actinin to increase its propensity to bind F‐actin. These results demonstrate a link between mechanical feedback and sarcomere protein homeostasis via PTMs of α‐actinin that exemplify how cardiomyocytes exhibit differential responses to the origin of force. The implications of sarcomere regulation governed by PTMs of α‐actinin are discussed with respect to cardiac atrophy and heart failure.

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Section: Discussionmentioning

confidence: 99%

“…Neonatal rat ventricular myocytes were isolated and cultured as previously described [ 26 , 63 ]. After NRVRMs were maintained in 10% FBS overnight, serum-free media was used in all subsequent experiments.…”

Section: Methodsmentioning

confidence: 99%

Cardiomyocyte external mechanical unloading activates modifications of α‐actinin differently from sarcomere‐originated unloading

et al. 2023

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Emerging biotechnologies for screening electromechanical signals of cardiomyocytes

Tang,

Sun,

Shi

et al. 2024

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Cardiac diseases threaten human health and burden the global healthcare system. Cardiomyocytes (CMs) are considered the ideal model for studying the signal transduction and regulation of cardiac systems. Based on the principle of the rhythmical beating process (excitation‒contraction coupling mechanism of CMs), investigating the mechanical and electrophysiological signals offered new hope for cardiac disease detection, prevention, and treatment. Considerable technological success has been achieved in electromechanical signal recording. However, most drug assessment platforms attach importance to high‐throughput and dynamic monitoring of mechanical or electrical signals while overlooking the measuring principles and physiological significance of the signal. In this review, the development of biosensing platforms for CMs, sensing principles, key measured parameters, measurement accuracy, and limitations are discussed. Additionally, various approaches for the stimulation and measurement of CMs in vitro are discussed to further elucidate the response of these cells to external stimuli. Furthermore, disease modeling and drug screening are used as examples to intuitively demonstrate the contribution of in vitro CM measurement platforms to the biomedical field, thereby further illustrating the challenges and prospects of these sensing platforms.

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P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function

Munoz,

Solis,

McCann

et al. 2024

Mol Cell Biochem

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Transthyretin deposition alters cardiomyocyte sarcomeric architecture, calcium transients, and contractile force

Cited by 4 publications

References 59 publications

Cardiomyocyte external mechanical unloading activates modifications of α‐actinin differently from sarcomere‐originated unloading

Cardiomyocyte external mechanical unloading activates modifications of α‐actinin differently from sarcomere‐originated unloading

Emerging biotechnologies for screening electromechanical signals of cardiomyocytes

P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function

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