Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil.

Benders, A.A.G.M.; Veerkamp, J.H.; Oosterhof, Arie; Jongen, Peter Joseph; Bindels, René J. M.; Smit, L.; Busch, H. F. M.; Wevers, Ron A.

doi:10.1172/jci117393

Cited by 66 publications

(71 citation statements)

References 41 publications

(31 reference statements)

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“…They also showed that the content of total Ca 21 ATPase protein and SERCA1 protein, measured both by immunoreactivity and by phosphorylation, was identical in the two sample populations, but that Ca 21 -stimulated ATPase activity in Brody muscle homogenates was reduced to only 50% of the activity found in comparable samples from normal patients. In cultured muscle cells from both patients in one of the families and controls, the sarcoplasmic Ca 21 concentration at rest and the increase in intracellular Ca 21 concentration after addition of acetylcholine were found to be the same [63]. Nevertheless, the time required to reach resting intracellular Ca 21 levels after Ca 21 release was increased several-fold in cells derived from these patients.…”

Section: P H Y S I O L O G I C a L B A S I S F O R B R O D Y D I S E mentioning

confidence: 85%

“…However, Benders et al [63] used an antibody specific against SERCA1, to demonstrate that 83% of the total Ca 21 ATPase in 10 Brody patients and control muscle homogenates was SERCA1. They also showed that the content of total Ca 21 ATPase protein and SERCA1 protein, measured both by immunoreactivity and by phosphorylation, was identical in the two sample populations, but that Ca 21 -stimulated ATPase activity in Brody muscle homogenates was reduced to only 50% of the activity found in comparable samples from normal patients.…”

Section: P H Y S I O L O G I C a L B A S I S F O R B R O D Y D I S E mentioning

confidence: 99%

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Ca²⁺ signalling and muscle disease

MacLennan

2000

European Journal of Biochemistry

218

155

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Transient elevations of intracellular Ca2+ play a signalling role in such complex cellular functions as contraction, secretion, fertilization, proliferation, metabolism, heartbeat and memory. However, prolonged elevation of Ca2+ above about 10 µm is deleterious to a cell and can activate apoptosis. In muscle, there is a narrow window of Ca2+ dysregulation in which abnormalities in Ca2+ regulatory proteins can lead to disease, rather than apoptosis. Key proteins in the regulation of muscle Ca2+ are the voltage‐dependent, dihydropyridine‐sensitive, l‐type Ca2+ channels located in the transverse tubule and Ca2+ release channels in the junctional terminal cisternae of the sarcoplasmic reticulum. Abnormalities in these proteins play a key role in malignant hyperthermia (MH), a toxic response to anesthetics, and in central core disease (CCD), a muscle myopathy. Sarco(endo)plasmic reticulum Ca2+ ATPases (SERCAs) return sarcoplasmic Ca2+ to the lumen of the sarcoplasmic reticulum. Loss of SERCA1a Ca2+ pump function is one cause of exercise‐induced impairment of the relaxation of skeletal muscle, in Brody disease. Phospholamban expressed in cardiac muscle and sarcolipin expressed in skeletal muscle regulate SERCA activity. Studies with knockout and transgenic mice show that gain of inhibitory function of phospholamban alters cardiac contractility and could be a causal feature in some cardiomyopathies. Calsequestrin, calreticulin, and a series of other acidic, lumenal, Ca2+ binding proteins provide a buffer for Ca2+ stored in the sarcoplasmic reticulum. Overexpression of cardiac calsequestrin leads to cardiomyopathy and ablation of calreticulin alters cardiac development.

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Section: P H Y S I O L O G I C a L B A S I S F O R B R O D Y D I S E mentioning

confidence: 85%

Section: P H Y S I O L O G I C a L B A S I S F O R B R O D Y D I S E mentioning

confidence: 99%

Ca²⁺ signalling and muscle disease

MacLennan

2000

European Journal of Biochemistry

218

155

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“…Functional studies on muscle samples from humans with Brody's disease have demonstrated that some patients exhibit reduced levels of SERCA1 protein content [105,106], while in other cases the levels of SERCA1 protein are unaltered, but there is a significant reduction (up to 80%) in the Ca 2+ pumping activity both in homogenates of muscle samples and in myotubes explanted from patients [99,106,107]. Chianina cattle pseudomyotonia, a disease similar to Brody's disease affecting cattle, is caused by the homozygous ATP2A1 p.R164H mutation [108].…”

Section: Brody's Diseasementioning

confidence: 99%

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

Treves

Jungbluth

Voermans

et al. 2017

Seminars in Cell & Developmental Biology

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a b s t r a c tThe physiological process by which Ca 2+ is released from the sarcoplasmic reticulum is called excitationcontraction coupling; it is initiated by an action potential which travels deep into the muscle fiber where it is sensed by the dihydropyridine receptor, a voltage sensing L-type Ca 2+ channel localized on the transverse tubules. Voltage-induced conformational changes in the dihydropyridine receptor activate the ryanodine receptor Ca 2+ release channel of the sarcoplasmic reticulum. The released Ca 2+ binds to troponin C, enabling contractile thick-thin filament interactions. The Ca 2+ is subsequently transported back into the sarcoplasmic reticulum by specialized Ca 2+ pumps (SERCA), preparing the muscle for a new cycle of contraction. Although other proteins are involved in excitation-contraction coupling, the mechanism described above emphasizes the unique role played by the two Ca 2+ channels (the dihydropyridine receptor and the ryanodine receptor), the SERCA Ca 2+ pumps and the exquisite spatial organization of the membrane compartments endowed with the proteins responsible for this mechanism to function rapidly and efficiently. Research over the past two decades has uncovered the fine details of excitation-contraction coupling under normal conditions while advances in genomics have helped to identify mutations in novel genes in patients with neuromuscular disorders. While it is now clear that many patients with congenital muscle diseases carry mutations in genes encoding proteins directly involved in Ca 2+ homeostasis, it has become apparent that mutations are also present in genes encoding for proteins not thought to be directly involved in Ca 2+ regulation. Ongoing research in the field now focuses on understanding the functional effect of individual mutations, as well as understanding the role of proteins not specifically located in the sarcoplasmic reticulum which nevertheless are involved in Ca 2+ regulation or excitation-contraction coupling. The principal challenge for the future is the identification of drug targets that can be pharmacologically manipulated by small molecules, with the ultimate aim to improve muscle function and quality of life of patients with congenital muscle disorders. The aim of this review is to give an overview of the most recent findings concerning Ca 2+ dysregulation and its impact on muscle function in patients with congenital muscle disorders due to mutations in proteins involved in excitation-contraction coupling and more broadly on Ca 2+ homeostasis.

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“…2 Biochemical and immunocytochemical studies in muscle biopsies from some patients with BD showed a marked reduction of Ca 2 þ uptake and Ca 2 þ ATPase activity in the sarcoplasmic reticulum of fast-twitch but not slow-twitch skeletal muscle fibres. 2,3 This was followed by the identification of pathogenic mutations in the ATP2A1 gene, encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca 2 þ ATPase, in a subset of patients with autosomal recessive BD. 4 Rare families with autosomal dominant inheritance have been reported, but in those families mutations in the ATP2A1 gene could not be found, further supporting genetic heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Autosomal dominant Brody disease cosegregates with a chromosomal (2;7)(p11.2;p12.1) translocation in an Italian family

et al. 2004

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Brody disease is a rare muscle disorder characterized by exercise-induced impairment in muscle relaxation, due to a markedly reduced influx of calcium ions in the sarcoplasmic reticulum. A subset of autosomal recessive families harbour mutations in the ATP2A1 gene, encoding the fast-twitch skeletal muscle sarcoplasmic reticulum Ca 2 þ ATPase (SERCA1). Rare autosomal dominant families have been described, in which ATP2A1 was excluded as the causative gene, further supporting genetic heterogeneity. We report four individuals from a three-generation Italian family with a clinical phenotype of Brody disease, in which linkage analysis excluded ATP2A1 as the responsible gene. The disease cosegregates in an autosomal dominant fashion with an apparently balanced constitutional chromosome translocation (2;7)(p11.2;p12.1), suggesting a causal relationship between the rearrangement and the phenotype. FISH analysis using YAC and PAC clones as probes refined the breakpoint regions to genomic segments of about 164 and 120 kb, respectively, providing a possible clue to pinpoint the location of a novel gene responsible for this rare muscle disorder.

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Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil.

Abstract: Brody's disease, i.e., sarcoplasmic reticulum (SR) Ca2+-dependent Mg2+-ATPase (Ca2+-ATPase) deficiency, is a rare inherited disorder of skeletal muscle function. Pseudo-myotonia is the most important clinical feature. SR Ca2+-AT-

Cited by 66 publications

References 41 publications

Ca²⁺ signalling and muscle disease

Ca²⁺ signalling and muscle disease

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

Autosomal dominant Brody disease cosegregates with a chromosomal (2;7)(p11.2;p12.1) translocation in an Italian family

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Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil.

Abstract: Brody's disease, i.e., sarcoplasmic reticulum (SR) Ca2+-dependent Mg2+-ATPase (Ca2+-ATPase) deficiency, is a rare inherited disorder of skeletal muscle function. Pseudo-myotonia is the most important clinical feature. SR Ca2+-AT-

Cited by 66 publications

References 41 publications

Ca2+ signalling and muscle disease

Ca2+ signalling and muscle disease

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

Autosomal dominant Brody disease cosegregates with a chromosomal (2;7)(p11.2;p12.1) translocation in an Italian family

Contact Info

Product

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Ca²⁺ signalling and muscle disease

Ca²⁺ signalling and muscle disease