Conduction abnormality in gap junction protein connexin45‐deficient embryonic stem cell‐derived cardiac myocytes

Egashira, Kensuke; Nishii, Kanae; Nakamura, Kei; Kumai, Madoka; Morimoto, Sachio; Shibata, Yosaburo

doi:10.1002/ar.a.20110

Cited by 27 publications

(16 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, Cx45-null mESC are morphologically similar to the wildtype and can readily differentiate into cells of the three germ layers following embryoid body formation [26]. One explanation for this lack of phenotype is that Cx43 is still expressed in Cx45-null mESC and may compensate for the loss of Cx45 [26].…”

Section: Similar To Cells From the Inner Cell Mass Undifferentiated mentioning

confidence: 88%

“…One explanation for this lack of phenotype is that Cx43 is still expressed in Cx45-null mESC and may compensate for the loss of Cx45 [26]. Interestingly, when Cx45-null mESC were injected into the blastocyst, they failed to form chimeric mice or post-implantation embryos.…”

Section: Similar To Cells From the Inner Cell Mass Undifferentiated mentioning

confidence: 89%

“…Interestingly, when Cx45-null mESC were injected into the blastocyst, they failed to form chimeric mice or post-implantation embryos. Subsequent studies of chimeric blastocysts cultured in vitro showed that Cx45-null mESC were unable to incorporate into the recipient inner cell mass [26]. Cx45 +/− heterozygous mutant mESC also show a decreased efficiency in forming chimeric mice [26].…”

Section: Similar To Cells From the Inner Cell Mass Undifferentiated mentioning

confidence: 98%

See 2 more Smart Citations

Role of Gap Junctions in Embryonic and Somatic Stem Cells

2008

View full text Add to dashboard Cite

Stem cells provide an invaluable tool to develop cell replacement therapies for a range of serious disorders caused by cell damage or degeneration. Much research in the field is focused on the identification of signals that either maintain stem cell pluripotency or direct their differentiation. Understanding how stem cells communicate within their microenvironment is essential to achieve their therapeutic potentials. Gap junctional intercellular communication (GJIC) has been described in embryonic stem cells (ES cells) and various somatic stem cells. GJIC has been implicated in regulating different biological events in many stem cells, including cell proliferation, differentiation and apoptosis. This review summarizes the current understanding of gap junctions in both embryonic and somatic stem cells, as well as their potential role in growth control and cellular differentiation.

show abstract

Section: Similar To Cells From the Inner Cell Mass Undifferentiated mentioning

confidence: 88%

Section: Similar To Cells From the Inner Cell Mass Undifferentiated mentioning

confidence: 89%

Section: Similar To Cells From the Inner Cell Mass Undifferentiated mentioning

confidence: 98%

See 1 more Smart Citation

Role of Gap Junctions in Embryonic and Somatic Stem Cells

2008

View full text Add to dashboard Cite

show abstract

“…and sarcomere length were simultaneously monitored using a fluorescence and contractility recording system (IonOptix) as described previously. 14 …”

Section: Fura-2 Loading and Simultaneous Measurements Of Fluorescencementioning

confidence: 99%

Knock-In Mouse Model of Dilated Cardiomyopathy Caused by Troponin Mutation

Cheng

Morimoto

Nishii

et al. 2007

Circulation Research

Self Cite

167

206

View full text Add to dashboard Cite

Abstract-We created knock-in mice in which a deletion of 3 base pairs coding for K210 in cardiac troponin (cTn)T found in familial dilated cardiomyopathy patients was introduced into endogenous genes. Membrane-permeabilized cardiac muscle fibers from mutant mice showed significantly lower Ca 2ϩ sensitivity in force generation than those from wild-type mice. Peak amplitude of Ca 2ϩ transient in cardiomyocytes was increased in mutant mice, and maximum isometric force produced by intact cardiac muscle fibers of mutant mice was not significantly different from that of wild-type mice, suggesting that Ca 2ϩ transient was augmented to compensate for decreased myofilament Ca 2ϩ sensitivity. Nevertheless, mutant mice developed marked cardiac enlargement, heart failure, and frequent sudden death recapitulating the phenotypes of dilated cardiomyopathy patients, indicating that global functional defect of the heart attributable to decreased myofilament Ca 2ϩ sensitivity could not be fully compensated by only increasing the intracellular Ca 2ϩ transient. We found that a positive inotropic agent, pimobendan, which directly increases myofilament Ca 2ϩ sensitivity, had profound effects of preventing cardiac enlargement, heart failure, and sudden death. These results verify the hypothesis that Ca 2ϩ desensitization of cardiac myofilament is the absolute cause of the pathogenesis of dilated cardiomyopathy associated with this mutation and strongly suggest that Ca 2ϩ sensitizers are beneficial for the treatment of dilated cardiomyopathy patients affected by sarcomeric regulatory protein mutations. (Circ Res. 2007;101:185-194.)Key Words: dilated cardiomyopathy Ⅲ troponin Ⅲ mutation Ⅲ calcium sensitivity Ⅲ knock-in mouse D ilated cardiomyopathy (DCM) is a disorder of cardiac muscle characterized by cardiac enlargement and systolic dysfunction and accounts for more than 10 000 deaths annually by heart failure and sudden death in the United States. 1-3 DCM is known to result from nongenetic insults, such as viruses, alcohol, toxins, and immunologic injury; however, recent genetic studies have revealed that mutations in genes for cytoskeletal (dystrophin, desmin, ␦-sarcoglycan), nuclear envelope (tafazzin and lamin A/C), and sarcomeric (cardiac actin, ␤-cardiac myosin heavy chain, ␣-tropomyosin, cardiac myosin-binding protein C, titin/connectin, cardiac troponin [cTn]T, cTnI, and cTnC) proteins are important causes of DCM, 4 and the incidence of the inherited DCM is thought to be 20% to 35%. [5][6][7] Cardiac muscle contraction is regulated through Ca 2ϩ binding to cardiac troponin complex localized on the thin filaments, 8 and DCM-causing mutations in troponin complex are associated with a malignant phenotype with a high incidence of premature cardiac death and heart transplantation. 9 Cardiac troponin complex consists of 3 components of distinct structure and function, cTnT, cTnI, and cTnC. cTnT has a structural role in anchoring troponin complex to the thin filaments through its binding to tropomyosin, cTnI inhibits the interaction ...

show abstract

“…The mechanical and electrical activation of the heart is in part dependent on the spatial distribution of GJs (22). Changes in GJ patterning and expression level can result in the development of arrhythmias in numerous cardiovascular diseases (23)(24)(25). The alteration in the expression level and spatial distribution of Cx43 in the hypertrophic myocardium suggests that this protein is influenced by ventricular remodeling (18).…”

Section: A B C D Ementioning

confidence: 99%

Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

Sun

Wang

Hao

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATP-sensitive K + (K ATP ) channel agonist was capable of reducing isoproterenol (Iso)-induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and left-ventricular weight, and plasma B-type natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcription-polymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The K ATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the K ATP channel agonist nicorandil. Addition of the K ATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43.In conclusion, the present study indicated that chronic use of K ATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43.

show abstract

Conduction abnormality in gap junction protein connexin45‐deficient embryonic stem cell‐derived cardiac myocytes

Cited by 27 publications

References 28 publications

Role of Gap Junctions in Embryonic and Somatic Stem Cells

Role of Gap Junctions in Embryonic and Somatic Stem Cells

Knock-In Mouse Model of Dilated Cardiomyopathy Caused by Troponin Mutation

Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

Contact Info

Product

Resources

About