Ryanodine Receptor Calcium Release Channel
Mixed Function Oxygenases
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Serial changes in sarcoplasmic reticulum gene expression in volume-overloaded cardiac hypertrophy in the rat: effect of an angiotensin II receptor antagonist. (1/309)This study was designed to clarify whether gene expression in the cardiac sarcoplasmic reticulum [sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, ryanodine receptor and calsequestrin] changes in accordance with left ventricular functional alterations in the volume-overloaded heart. Further, the effect of the angiotensin II type 1 receptor antagonist, TCV-116, on the expression of these genes was also evaluated. Left ventricular fractional shortening was significantly increased at 7 days, had returned to control levels at 21 days, and had significantly decreased at 35 days after the shunt operation, compared with sham-operated rats. The level of SERCA mRNA was significantly decreased at both 21 days and 35 days after the shunt operation. The levels of ryanodine receptor and phospholamban mRNAs were significantly decreased at 35 days in shunt-operated rats. The decrease in the SERCA mRNA level preceded the development of cardiac dysfunction. The levels of SERCA and ryanodine receptor mRNAs were correlated positively with left ventricular fractional shortening (r=0.73, P<0.0001 and r=0.61, P<0.01 respectively). Attenuation of the decrease in left ventricular fractional shortening occurred on treatment with TCV-116. After the treatment with TCV-116, the levels of SERCA and phospholamban mRNAs were restored to the respective values in sham-operated rats. Ryanodine receptor mRNA levels remained unchanged after treatment with TCV-116. These results indicate that the down-regulation of SERCA and ryanodine receptor mRNA levels may be related to cardiac dysfunction in the volume-overloaded heart. In addition, treatment with an angiotensin II receptor antagonist may restore the altered sarcoplasmic reticulum mRNA levels to control levels, and this may result in attenuation of the functional impairment in the volume-overloaded heart. (+info)
Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling. (2/309)OBJECTIVES: We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation. BACKGROUND: Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear. METHODS: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. RESULTS: The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation. CONCLUSIONS: L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation. (+info)
Reduced sodium pump alpha1, alpha3, and beta1-isoform protein levels and Na+,K+-ATPase activity but unchanged Na+-Ca2+ exchanger protein levels in human heart failure. (3/309)BACKGROUND: Cardiac glycosides initiate an increase in force of contraction by inhibiting the sarcolemmal sodium pump (Na+, K+-ATPase), thereby decreasing Ca2+ extrusion by the Na+-Ca2+ exchanger, which increases the cellular content of Ca2+. In patients with heart failure the sensitivity toward cardiac glycosides is enhanced. METHODS AND RESULTS: Because the inotropic effect of cardiac glycosides may be a function of the sodium pump and Na+-Ca2+ exchanger (NCE) expression levels, the present study aimed to investigate protein expression of both transporters (immunoblot with specific antibodies against the sodium pump catalytic alpha1-, alpha2-, alpha3-, and glycoprotein beta1-isoforms and against NCE) in left ventricle from failing (heart transplantations, New York Heart Association class IV, n=21) compared with nonfailing (donor hearts, NF, n=22) human myocardium. The density of 3H-ouabain-binding sites (Bmax) and the Na+,K+-ATPase activity were also measured. In NYHA class IV, protein levels of Na+,K+-ATPase alpha1- (0.62+/-0.06 of control), alpha3- (0.70+/-0.09), and beta1- (0.61+/-0.04) but not alpha2-isoforms were significantly reduced (P<0.01), whereas levels of NCE (0.92+/-0.13 of control) and calsequestrin (0.98+/-0.06) remained unchanged. Both Na+,K+-ATPase activity (NF: 1.9+/-0.29; NYHA class IV: 1.1+/-0.17 micromol ATP/min per milligram of protein) and the 3H-ouabain binding sites (Bmax NF: 15.9+/-1.9 pmol/mg protein; NYHA class IV: 9.7+/-1.5) were reduced in NYHA class IV and correlated significantly to each other (r2=0. 73; P<0.0001), as did beta1-subunit expression. In left ventricular papillary muscle strips from NYHA class IV compared with nonfailing tissue the Na+-channel modulator BDF 9198 exerted an increase in force of contraction with unchanged effectiveness but enhanced potency. CONCLUSIONS: The enhanced sensitivity of failing human myocardium toward cardiac glycosides may be, at least in part, attributed to a reduced protein expression and activity of the sarcolemmal Na+,K+-ATPase without a change in Na+-Ca2+ exchanger protein expression. (+info)
Analysis of calsequestrin gene expression using green fluorescent protein in Caenorhabditis elegans. (4/309)The calsequestrin gene of Caenorhabditis elegans is expressed in body-wall muscle cells during muscle development. In order to study the body-wall muscle specific regulation of the calsequestrin gene expression, approximately 2 kb upstream sequences of the calsequestrin gene were analyzed. Transcriptional fusion constructs utilizing green fluorescent protein as a reporter gene were made and microinjected to produce germ-line transformed transgenic C. elegans. The expression of green fluorescent protein was observed in the body-wall muscles of live transgenic animals under fluorescence microscopy. Deletion analyses of upstream sequences have revealed a putative promoter sequence and a regulatory element which appeared to enhance reporter gene expression. Both sequence elements are juxtaposed to constitute a 260 bp regulatory region approximately 260 bp upstream from the putative translational initiation codon. Several possible binding sites for transcription factors were identified including the sites for YY1 and NF-W2, a muscle specific zinc finger transcription factor, and an ubiquitous enhancer binding protein, respectively. Interestingly, this region also contains a 20 bp sequence element identical to those found in the mouse dystrophin gene, which suggests a possible role of this regulatory region in muscle specific gene regulation. (+info)
Subunit expression of the cardiac L-type calcium channel is differentially regulated in diastolic heart failure of the cardiac allograft. (5/309)BACKGROUND: Left ventricular diastolic dysfunction is a major cause of cardiac allograft failure. Multimeric L-type calcium channels (alpha1-, alpha2/delta-, and beta-subunits) are essential for excitation/contraction coupling in the heart. Their gene expression was studied in allografts that developed diastolic heart failure. METHODS AND RESULTS: mRNA levels of calcium channel subunits were measured by competitive reverse transcriptase-polymerase chain reaction in microbiopsy samples from the interventricular septum. Size and tissue variabilities between biopsy samples were assessed by determination of cardiac calsequestrin mRNA levels. In the cardiac allografts studied, mRNA levels in microbiopsy samples were considered to represent left ventricular gene expression, because septal and left ventricular gene expression in Northern blots was equivalent, and left ventricles contracted homogeneously. Biopsy samples (n=72) were taken from allografts with normal left ventricular end-diastolic pressure (LVEDP; 8 to 13 mm Hg; n=30), moderately elevated LVEDP (14 to 18 mm Hg; n=26), and elevated LVEDP (19 to 28 mm Hg; n=16). Increased LVEDP was related to slowed diastolic relaxation determined by the time constant tau (r2=0.86), whereas systolic performance (dP/dt; ejection fraction) was preserved. With increasing LVEDP, mRNA levels of the pore-forming alpha1c-subunit (n=15) and of the regulatory alpha2/delta-subunit (n=17) remained unchanged but decreased exponentially (r2=-0.83) for the regulatory beta-subunit (n=40). Compared with cardiac allografts with normal LVEDP (n=15), beta-subunit mRNA level was reduced by 75% at elevated LVEDP (n=9; P=0.012). In an explanted, diastolically failing cardiac allograft, beta-subunit expression was reduced correspondingly by 72% and 76% on the mRNA level in septal and left ventricular myocardium and by 80% on the protein level. CONCLUSIONS: The downregulated expression of the calcium channel beta-subunit might contribute to altered calcium handling in diastolically failing cardiac allografts. (+info)
Defective beta-adrenergic receptor signaling precedes the development of dilated cardiomyopathy in transgenic mice with calsequestrin overexpression. (6/309)Calsequestrin is a high capacity Ca(2+)-binding protein in the junctional sarcoplasmic reticulum that forms a quaternary complex with junctin, triadin, and the ryanodine receptor. Transgenic mice with cardiac-targeted calsequestrin overexpression show marked suppression of Ca(2+)-induced Ca(2+) release, myocyte hypertrophy, and premature death by 16 weeks of age (Jones, L. R., Suzuki, Y. J., Wang, W., Kobayashi, Y. M., Ramesh, V., Franzini-Armstrong, C., Cleemann, L., and Morad, M. (1998) J. Clin. Invest. 101, 1385-1393). To investigate whether alterations in intracellular Ca(2+) trigger changes in the beta-adrenergic receptor pathway, we studied calsequestrin overexpressing transgenic mice at 7 and 14 weeks of age. As assessed by echocardiography, calsequestrin mice at 7 weeks showed mild left ventricular enlargement, mild decreased fractional shortening with increased wall thickness. By 14 weeks, the phenotype progressed to marked left ventricular enlargement and severely depressed systolic function. Cardiac catheterization in calsequestrin mice revealed markedly impaired beta-adrenergic receptor responsiveness in both 7- and 14- week mice. Biochemical analysis in 7- and 14-week mice showed a significant decrease in total beta-adrenergic receptor density, adenylyl cyclase activity, and the percent high affinity agonist binding, which was associated with increased beta-adrenergic receptor kinase 1 levels. Taken together, these data indicate that alterations in beta-adrenergic receptor signaling precede the development of overt heart failure in this mouse model of progressive cardiomyopathy. (+info)
Characterization of the binding and phosphorylation of cardiac calsequestrin by epsilon protein kinase C. (7/309)In this study, we report the cloning of the rat cardiac isoform of calsequestrin on the basis of its interaction with an epsilonprotein kinase C-unique sequence (epsilonV1) derived form the epsilonprotein kinase C regulatory domain. Calsequestrin binds activated epsilonprotein kinase C holoenzyme better than the inactive enzyme and nearly three times better than other protein kinase C isozymes. The interaction between epsilonprotein kinase C and calsequestrin is mediated by sequences in both the regulatory and kinase domains of the epsilonprotein kinase C. Finally, we show that calsequestrin is an epsilonprotein kinase C substrate in vitro and protein kinase C phosphorylation of calsequestrin leads to a decreased binding of epsilonprotein kinase C to calsequestrin. (+info)
Heterogeneous transmural gene expression of calcium-handling proteins and natriuretic peptides in the failing human heart. (8/309)OBJECTIVE: Human heart failure is associated with a disturbed intracellular calcium (Ca2+) homeostasis. In this regard, ventricular wall stress is considered to be a determinant for expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a). In the present study, we analyzed the transmural protein and/or mRNA levels of SERCA2a, other Ca(2+)-handling proteins, and of atrial and brain natriuretic peptides (ANP and BNP) in the human heart. METHODS: Subepicardial (epi), midmyocardial (mid), and subendocardial (endo) sections of the left ventricular free wall from end-stage failing (n = 17) and nonfailing (n = 5) human hearts were analyzed by Western blot for immunoreactive protein levels of SERCA2a, phospholamban (PLN), and calsequestrin (CS). Subepi- and subendocardial sections were analyzed by Northern blot for steady-state mRNA levels of SERCA2a, Na(+)-Ca2+ exchanger (NCX1), ANP, and BNP. RESULTS: SERCA2a protein and mRNA levels were reduced by 40 +/- 5% (P < 0.01) and 25 +/- 7% (P < 0.05) in endo compared to epi in the failing heart and by 27 +/- 14% and 16 +/- 12% (non-significant) in the nonfailing heart, respectively. PLN protein levels were reduced by 23 +/- 6% (P < 0.05) in endo compared to epi in the failing heart and by 17 +/- 25% (non-significant) in the nonfailing heart, whereas CS protein levels and NCX1 mRNA levels were similar across the left ventricular wall. Strikingly, in the failing heart, both BNP and ANP mRNA levels were upregulated predominantly in endo. CONCLUSIONS: In the failing human heart, SERCA2a and PLN, as well as natriuretic peptides but not CS and NCX1 are differentially expressed across the left ventricular wall, implicating (1) different susceptibility of subendocardium and subepicardium to factors affecting expression of these proteins and (2) differences in regulation of the distinct calcium-cycling proteins. (+info)
Tachycardia, ventricular can be classified into several types based on its duration and the presence of other symptoms. These include:
1. Paroxysmal ventricular tachycardia (PVT): This is a rapid heart rate that occurs in episodes lasting less than 30 seconds and may be accompanied by palpitations, shortness of breath, or dizziness.
2. Sustained ventricular tachycardia: This is a rapid heart rate that persists for more than 30 seconds and may require medical intervention to return the heart to normal rhythm.
3. Ventricular fibrillation (VF): This is a life-threatening condition in which the ventricles are unable to pump blood effectively due to rapid, disorganized electrical activity.
Symptoms of tachycardia, ventricular may include:
* Palpitations or rapid heartbeat
* Shortness of breath
* Dizziness or lightheadedness
* Chest pain or discomfort
* Fatigue or weakness
Diagnosis of tachycardia, ventricular is typically made based on a physical examination, medical history, and results of diagnostic tests such as electrocardiogram (ECG), echocardiogram, or stress test. Treatment options may include medications to regulate heart rhythm, cardioversion to restore normal heart rhythm, and in some cases, implantation of a cardioverter-defibrillator (ICD) to prevent sudden death.
In summary, tachycardia, ventricular is a rapid heart rate that originates in the ventricles and can be caused by a variety of conditions. It is important to seek medical attention if symptoms persist or worsen over time. With proper diagnosis and treatment, it is possible to manage the condition and improve quality of life.
Types of Immunoproliferative Disorders:
1. Lymphoproliferative Disorders: These are characterized by the excessive proliferation of lymphocytes, a type of immune cell. Examples include lymphoma, Hodgkin's disease, and non-Hodgkin's lymphoma.
2. Myeloproliferative Disorders: These are characterized by the excessive proliferation of myeloid cells, such as white blood cells, red blood cells, and platelets. Examples include polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
3. Autoimmune Disorders: These are characterized by the immune system attacking the body's own tissues. Examples include rheumatoid arthritis, lupus, and multiple sclerosis.
Causes and Risk Factors:
Immunoproliferative disorders can be caused by a variety of factors, including genetic mutations, infections, and exposure to certain chemicals or toxins. Some risk factors for immunoproliferative disorders include:
1. Genetic predisposition
2. Exposure to certain viruses, such as human T-lymphotropic virus (HTLV) and Epstein-Barr virus (EBV)
3. Exposure to certain chemicals or toxins, such as benzene and certain pesticides
4. Weakened immune system due to disease or medication
5. Age, with older adults being more susceptible to certain types of immunoproliferative disorders
The symptoms of immunoproliferative disorders can vary depending on the specific type and severity of the condition. Some common symptoms include:
1. Swollen lymph nodes
4. Weight loss
5. Night sweats
6. Skin rashes or lesions
7. Joint pain or swelling
8. Muscle weakness
9. Nervous system problems, such as numbness or tingling in the hands and feet
10. Swollen spleen
The treatment of immunoproliferative disorders depends on the specific type and severity of the condition. Some common treatments include:
1. Medications to suppress the immune system, such as corticosteroids and immunosuppressive drugs
2. Antiviral medications to treat infections that may be contributing to the condition
3. Chemotherapy to reduce the number of abnormal cells in the body
4. Radiation therapy to reduce the size of swollen lymph nodes or other affected tissues
5. Plasmapheresis, a process that removes abnormal antibodies from the blood
6. Bone marrow transplantation, which may be considered for some patients with severe forms of the condition.
The prognosis for immunoproliferative disorders varies depending on the specific type and severity of the condition. In general, the prognosis is good for patients who receive prompt and appropriate treatment, and who have a mild form of the condition. However, the prognosis is poorer for patients with severe or aggressive forms of the condition, and those who do not respond well to treatment.
There is currently no known way to prevent immunoproliferative disorders. However, early detection and treatment can help improve outcomes. Regular follow-up with a healthcare provider is important for patients with risk factors or symptoms of these conditions.
Catecholaminergic polymorphic ventricular tachycardia
Ryanodine receptor 1
Alpha blockade potentiates CPVT therapy in calsequestrin-mutant mice. | Heart Rhythm;11(8): 1471-9, 2014 Aug. | MEDLINE |...
CASQ2 gene: MedlinePlus Genetics
Congenital Myopathies Clinical Presentation: History, Nemaline Rod Myopathy, Core Myopathy
Research Goals - Karl Pfeifer Lab | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
skeletal muscle tissue development Antibodies | Invitrogen ...
A Mechanistic Clinical Trial Using ( R)- Versus (S)-Propafenone to Test RyR2 (Ryanodine Receptor) Inhibition for the Prevention...
Figures and data in Transverse tubule remodeling enhances Orai1-dependent Ca2+ entry in skeletal muscle | eLife
ugt1a10 gene|ugt1a10 gene|C1421323|udp glucuronosyltransferase 1 family, polypeptide a10|gngm
Hund Rudy 2004 | Interagency Modeling and Analysis Group
Pharos : Target Details - CASQ2
Health Psychology Research (HPR) - Research output - the University of Groningen research portal
OPUS 4 | 570 Biowissenschaften; Biologie
Find Research outputs - UTMB Health Research Expert Profiles
NCIt Code SwissProt ID NCIt Preferred Name
NDF-RT Code NDF-RT Name
Kitchen Remodeling L A, Toilet Remodel La, Santa Monica | LUD
Calreticulin Recombinant Protein
Cardiac sodium channel, its mutations and their spectrum of arrhythmia phenotypes
MESH TREE NUMBER CHANGES - 2001 MeSH
Tropomodulin | Profiles RNS
clima kissimmee - Tetra-Bio Beijing Tetrahedron Biotechnology Co., Ltd.
These Beating Mini-hearts Could Save Big Bucks-and Maybe Lives - Medera Incorporation
- Disruption of calcium homeostasis and arrhythmogenesis induced by mutations in the cardiac ryanodine receptor and calsequestrin. (medlineplus.gov)
- Membrane and intracellular systems (L-type calcium channels, ryanodine receptor, calsequestrin) regulate the supply of calcium to contractile proteins throughout contraction. (lookupdesign.net)
- Within myocytes, calsequestrin 2 is located in a cell structure called the sarcoplasmic reticulum, which acts as a storage center for calcium ions. (medlineplus.gov)
- In response to certain signals, calcium ions stored by calsequestrin 2 in the sarcoplasmic reticulum are released into the surrounding cell fluid (the cytoplasm). (medlineplus.gov)
- A lack of properly functioning calsequestrin 2 may also affect regulation of the RYR2 channel, allowing calcium ions to "leak" out of the sarcoplasmic reticulum. (medlineplus.gov)
- Alpha blockade potentiates CPVT therapy in calsequestrin-mutant mice. (bvsalud.org)
- Calsequestrin is the major Ca 2+ binding protein in the sarcoplasmic reticulum (SR), serves as the main Ca 2+ storage and buffering protein and is an important regulator of Ca 2+ release channels in both skeletal and cardiac muscle. (nih.gov)
- Recent studies reveal new insights on calsequestrin trafficking, Ca 2+ binding, protein evolution, protein-protein interactions, stress responses and the molecular basis of related human muscle disease, including catecholaminergic polymorphic ventricular tachycardia (CPVT). (nih.gov)
- Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. (nih.gov)
- Disruption of calcium homeostasis and arrhythmogenesis induced by mutations in the cardiac ryanodine receptor and calsequestrin. (medlineplus.gov)
- The protein encoded by this gene specifies the cardiac muscle family member of the calsequestrin family. (nih.gov)
- Understand the role of cardiac calsequestrin in normal heart development and function. (nih.gov)