The disorders of the calcium release unit of skeletal muscles: what have we learned from mouse models?

Canato, Marta; Capitanio, Paola; Reggiani, Carlo; Cancellara, Lina

doi:10.1007/s10974-014-9396-7

Cited by 13 publications

(10 citation statements)

References 63 publications

(86 reference statements)

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“…The heater organ is filled with SR membranous network surrounded by many mitochondria; continuous leak and reuptake of Ca 2+ by SERCA leads to heat generation [42–46]. The involvement Ca 2+ cycling in heat production is also observed in a pathological condition called “malignant hyperthermia (MH)”, caused by a mutation of the ryanodine receptor that results in uncontrolled Ca 2+ leak from the SR activating SERCA and heat production [47, 48]. Muscle-based Ca 2+ cycling in thermogenesis was suggested in cold acclimatized birds [49–51].…”

Section: Sr Ca2+ Cycling Plays a Role In Muscle Thermogenesismentioning

confidence: 99%

Sarcolipin is a novel regulator of muscle metabolism and obesity

Maurya

Periasamy

2015

Pharmacological Research

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Obesity is increasing at an alarming rate, both in adults and adolescents, across the globe due to increased consumption of caloric rich diet. Obesity and its associated complications appear to be major contributing factors not only to diabetes/heart disease but also to cancer, and neurological diseases causing a huge burden on the health care system. To date, there are no effective treatments to reduce weight gain, other than caloric restriction and exercise which are often difficult to enforce. There are very few drugs available for treating obesity and those that are available only reduce obesity by ~10%. Identifying mechanisms to increase energy expenditure, on top of the increase elicited by exercise, would be more beneficial to control weight gain. The purpose of this review is to highlight the role of sarcolipin (SLN), a regulator of SERCA pump, in muscle thermogenesis and metabolism. We will further discuss if enhancing SLN activity could be an effective mechanism to increase energy expenditure and control weight gain. We will also discuss the merits of adaptive thermogenesis in muscle and brown fat as potential mechanisms to increase energy expenditure during caloric overload. That said, there is still a great need for further research into the mechanism of diet induced thermogenesis and its relevance to overall metabolism and obesity.

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Section: Sr Ca2+ Cycling Plays a Role In Muscle Thermogenesismentioning

confidence: 99%

Sarcolipin is a novel regulator of muscle metabolism and obesity

Maurya

Periasamy

2015

Pharmacological Research

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“…A fulminant MH syndrome is characterized by an uncontrolled increase in myoplasmic free calcium (Ca 2+ ) that leads to increased metabolic rate and subsequently results in hyperthermia and muscle rigidity 2‐4 . This energetic crisis can be triggered by volatile anesthetics, depolarizing muscle relaxants (eg, succinylcholine), intense exercise, and exposure to elevated environmental temperatures 5 . The prevalence in the human population of known MH‐causative mutations is 1:2750, 6 with variants in the ryanodine receptor 1 gene ( RYR1 ) being responsible for the majority of MH cases 7 .…”

Section: Introductionmentioning

confidence: 99%

Sex‐specific alterations in whole body energetics and voluntary activity in heterozygous R163C malignant hyperthermia‐susceptible mice

et al. 2020

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Malignant hyperthermia (MH) is characterized by induction of skeletal muscle hyperthermia in response to a dysregulated increase in myoplasmic calcium. Although altered energetics play a central role in MH, MH‐susceptible humans and mouse models are often described as having no phenotype until exposure to a triggering agent. The purpose of this study was to determine the influence of the R163C ryanodine receptor 1 mutation, a common MH mutation in humans, on energy expenditure, and voluntary wheel running in mice. Energy expenditure was measured by indirect respiration calorimetry in wild‐type (WT) and heterozygous R163C (HET) mice over a range of ambient temperatures. Energy expenditure adjusted for body weight or lean mass was increased (P < .05) in male, but not female, HET mice housed at 22°C or when housed at 28°C with a running wheel. In female mice, voluntary wheel running was decreased (P < .05) in the HET vs WT animals when analyzed across ambient temperatures. The thermoneutral zone was also widened in both male and female HET mice. The results of the study show that the R163C mutations alters energetics even at temperatures that do not typically induce MH.

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“…Interestingly, the phenotype affects predominantly fast muscles [extensor digitorum longus (EDL) muscle but not soleus]. The phenotypes of Casq1 −/− and Ryr1-mutant mice overlap strikingly (see Table 3; Canato et al, 2015), including increased mitochondrial damage and elevated ROS levels that can be ameliorated with antioxidant administration (Durham et al, 2008;Paolini et al, 2015). Of note, electron-dense aggregates ( presumed by the authors to be CASQ1) were observed by electron-microscopy analysis of Ryr1 I4895T/+ mice (Boncompagni et al, 2010), further highlighting the overlapping phenotypes of congenital myopathies.…”

Section: Recessive Ryr1 Modelsmentioning

confidence: 99%

Cored in the act: the use of models to understand core myopathies

Fusto

Moyle

Gilbert

et al. 2019

Disease Models &Amp; Mechanisms

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The core myopathies are a group of congenital myopathies with variable clinical expressionranging from early-onset skeletal-muscle weakness to later-onset disease of variable severitythat are identified by characteristic 'core-like' lesions in myofibers and the presence of hypothonia and slowly or rather non-progressive muscle weakness. The genetic causes are diverse; central core disease is most often caused by mutations in ryanodine receptor 1 (RYR1), whereas multi-minicore disease is linked to pathogenic variants of several genes, including selenoprotein N (SELENON), RYR1 and titin (TTN). Understanding the mechanisms that drive core development and muscle weakness remains challenging due to the diversity of the excitation-contraction coupling (ECC) proteins involved and the differential effects of mutations across proteins. Because of this, the use of representative models expressing a mature ECC apparatus is crucial. Animal models have facilitated the identification of disease progression mechanisms for some mutations and have provided evidence to help explain genotype-phenotype correlations. However, many unanswered questions remain about the common and divergent pathological mechanisms that drive disease progression, and these mechanisms need to be understood in order to identify therapeutic targets. Several new transgenic animals have been described recently, expanding the spectrum of core myopathy models, including mice with patient-specific mutations. Furthermore, recent developments in 3D tissue engineering are expected to enable the study of core myopathy disease progression and the effects of potential therapeutic interventions in the context of human cells. In this Review, we summarize the current landscape of core myopathy models, and assess the hurdles and opportunities of future modeling strategies.

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The disorders of the calcium release unit of skeletal muscles: what have we learned from mouse models?

Cited by 13 publications

References 63 publications

Sarcolipin is a novel regulator of muscle metabolism and obesity

Sarcolipin is a novel regulator of muscle metabolism and obesity

Sex‐specific alterations in whole body energetics and voluntary activity in heterozygous R163C malignant hyperthermia‐susceptible mice

Cored in the act: the use of models to understand core myopathies

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