Core skeletal muscle ryanodine receptor calcium release complex

Dulhunty, Angela F.; Wei-LaPierre, Lan; Beard, Nicole A.

doi:10.1111/1440-1681.12676

Cited by 24 publications

(19 citation statements)

References 94 publications

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“…; Schneider, ; Dulhunty et al . ). Centronuclear myopathies (CNMs) encompass a group of inherited diseases that yield heterogeneous features in terms of age of onset and muscle weakness severity and progression, with all of them being associated with the presence of nuclei in a central position within the muscle fibres.…”

Section: Introductionmentioning

confidence: 97%

Impaired excitation–contraction coupling in muscle fibres from the dynamin2^R465W mouse model of centronuclear myopathy

Kutchukian

Szentesi

Allard

et al. 2017

The Journal of Physiology

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Mutations in the gene encoding dynamin 2 (DNM2) are responsible for autosomal dominant centronuclear myopathy (AD-CNM). We studied the functional properties of Ca signalling and excitation-contraction (EC) coupling in muscle fibres isolated from a knock-in (KI) mouse model of the disease, using confocal imaging and the voltage clamp technique. The transverse-tubule network organization appeared to be unaltered in the diseased fibres, although its density was reduced by ∼10% compared to that in control fibres. The density of Ca current through CaV1.1 channels and the rate of voltage-activated sarcoplasmic reticulum Ca release were reduced by ∼60% and 30%, respectively, in KI vs. control fibres. In addition, Ca release in the KI fibres reached its peak value 10-50 ms later than in control ones. Activation of Ca transients along the longitudinal axis of the fibres was more heterogeneous in the KI than in the control fibres, with the difference being exacerbated at intermediate membrane voltages. KI fibres exhibited spontaneous Ca release events that were almost absent from control fibres. Overall, the results of the present study demonstrate that Ca signalling and EC coupling exhibit a number of dysfunctions likely contributing to muscle weakness in DNM2-related AD-CNM.

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Section: Introductionmentioning

confidence: 97%

Impaired excitation–contraction coupling in muscle fibres from the dynamin2^R465W mouse model of centronuclear myopathy

Kutchukian

Szentesi

Allard

et al. 2017

The Journal of Physiology

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“…Hence, RyR1 plays a crucial role in the excitation-contraction coupling of skeletal muscle (e.g. 11 – 13 ). Mutations in the RyR1 isoform have been linked to malignant hyperthermia and central core disease 2 , 3 .…”

Section: Introductionmentioning

confidence: 99%

In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways

Heinz

Kopeć

Groot

et al. 2018

Sci Rep

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The ryanodine receptor 1 is a large calcium ion channel found in mammalian skeletal muscle. The ion channel gained a lot of attention recently, after multiple independent authors published near-atomic cryo electron microscopy data. Taking advantage of the unprecedented quality of structural data, we performed molecular dynamics simulations on the entire ion channel as well as on a reduced model. We calculated potentials of mean force for Ba2+, Ca2+, Mg2+, K+, Na+ and Cl− ions using umbrella sampling to identify the key residues involved in ion permeation. We found two main binding sites for the cations, whereas the channel is strongly repulsive for chloride ions. Furthermore, the data is consistent with the model that the receptor achieves its ion selectivity by over-affinity for divalent cations in a calcium-block-like fashion. We reproduced the experimental conductance for potassium ions in permeation simulations with applied voltage. The analysis of the permeation paths shows that ions exit the pore via multiple pathways, which we suggest to be related to the experimental observation of different subconducting states.

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“…Ca 2+ release from RyRs is activated through charge-dependent conformational changes of the dihydropyridine receptor (DHPR) 13,15) . Calsequestrin (CSQ) is located in the SR lumen, and modulates the sensitivity of RyRs 16,17) . Dephosphorylated FKBP12 (composed of FK-506 binding proteins) is associated with a decreased probability and duration of RyR opening, which impairs SR Ca 2+ release 18) .…”

Section: Structural Components Of Ca 2+ Transport Across Organelle Mementioning

confidence: 99%

Mitochondrial calcium regulation during and following contractions in skeletal muscle

Eshima

Poole

Kano

2018

JPFSM

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In skeletal muscle, resting cytosolic Ca 2+ concentration ([Ca 2+ ] cyto) homeostasis is exquisitely regulated by Ca 2+ transport across the sarcolemmal, mitochondrial and sarcoplasmic reticulum (SR) membranes. Specifically, skeletal muscle contractile function is critically dependent on effective SR Ca 2+ handling. However, more recent studies have revealed that mitochondria are essentially involved in [Ca 2+ ] cyto homeostasis during and following muscle contractions. We recently provided substantial support for the mitochondria as a major site for Ca 2+ sequestration in skeletal muscle during recovery from fatiguing tetanic contractions under in vivo conditions. This review provides an overview of the role of skeletal muscle mitochondria in [Ca 2+ ] cyto regulation in vivo during and following muscle contractions.

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Core skeletal muscle ryanodine receptor calcium release complex

Cited by 24 publications

References 94 publications

Impaired excitation–contraction coupling in muscle fibres from the dynamin2^R465W mouse model of centronuclear myopathy

Impaired excitation–contraction coupling in muscle fibres from the dynamin2^R465W mouse model of centronuclear myopathy

In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways

Mitochondrial calcium regulation during and following contractions in skeletal muscle

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Core skeletal muscle ryanodine receptor calcium release complex

Cited by 24 publications

References 94 publications

Impaired excitation–contraction coupling in muscle fibres from the dynamin2R465W mouse model of centronuclear myopathy

Impaired excitation–contraction coupling in muscle fibres from the dynamin2R465W mouse model of centronuclear myopathy

In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways

Mitochondrial calcium regulation during and following contractions in skeletal muscle

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Product

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Impaired excitation–contraction coupling in muscle fibres from the dynamin2^R465W mouse model of centronuclear myopathy

Impaired excitation–contraction coupling in muscle fibres from the dynamin2^R465W mouse model of centronuclear myopathy