Mechanics and energetics in cardiac arrhythmias and heart failure

Bers, Donald M.; Kohl, Peter; Chen‐Izu, Ye

doi:10.1113/jp279385

Cited by 1 publication

(1 citation statement)

References 17 publications

(17 reference statements)

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“…In cardiomyocytes Ca 2+ entry from the extracellular space and release by the SR activates contraction of myofibrils. Ca 2+ entry and release are coupled by a mechanism known as CICR [75]: (i) upon membrane depolarization, a small influx of Ca 2+ enters through the L-type Ca 2+ channel (Ca.V. 1.2), also known as DHPR, located mainly in the T-tubule membranes, then (ii) Ca 2+ entry triggers RYR2 to open allowing release of a larger amount of Ca 2+ from the SR in the form of discrete release events called Ca 2+ sparks [76].…”

Section: Eccoupling System Modificationsmentioning

confidence: 99%

Ageing Causes Ultrastructural Modification to Calcium Release Units and Mitochondria in Cardiomyocytes

d’Onofrio

Fonso

Protasi

et al. 2021

IJMS

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Ageing is associated with an increase in the incidence of heart failure, even if the existence of a real age-related cardiomyopathy remains controversial. Effective contraction and relaxation of cardiomyocytes depend on efficient production of ATP (handled by mitochondria) and on proper Ca2+ supply to myofibrils during excitation–contraction (EC) coupling (handled by Ca2+ release units, CRUs). Here, we analyzed mitochondria and CRUs in hearts of adult (4 months old) and aged (≥24 months old) mice. Analysis by confocal and electron microscopy (CM and EM, respectively) revealed an age-related loss of proper organization and disposition of both mitochondria and EC coupling units: (a) mitochondria are improperly disposed and often damaged (percentage of severely damaged mitochondria: adults 3.5 ± 1.1%; aged 16.5 ± 3.5%); (b) CRUs that are often misoriented (longitudinal) and/or misplaced from the correct position at the Z line. Immunolabeling with antibodies that mark either the SR or T-tubules indicates that in aged cardiomyocytes the sarcotubular system displays an extensive disarray. This disarray could be in part caused by the decreased expression of Cav-3 and JP-2 detected by western blot (WB), two proteins involved in formation of T-tubules and in docking SR to T-tubules in dyads. By WB analysis, we also detected increased levels of 3-NT in whole hearts homogenates of aged mice, a product of nitration of protein tyrosine residues, recognized as marker of oxidative stress. Finally, a detailed EM analysis of CRUs (formed by association of SR with T-tubules) points to ultrastructural modifications, i.e., a decrease in their frequency (adult: 5.1 ± 0.5; aged: 3.9 ± 0.4 n./50 μm2) and size (adult: 362 ± 40 nm; aged: 254 ± 60 nm). The changes in morphology and disposition of mitochondria and CRUs highlighted by our results may underlie an inefficient supply of Ca2+ ions and ATP to the contractile elements, and possibly contribute to cardiac dysfunction in ageing.

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Section: Eccoupling System Modificationsmentioning

confidence: 99%