Connexins in mammalian heart function

Gros, Daniël; Jongsma, Habo J.

doi:10.1002/bies.950180907

Cited by 268 publications

(165 citation statements)

References 58 publications

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“…17,18,33 A relationship between gap junctional area and conductance has also been demonstrated in newly forming connections between isolated myocytes in vitro, 34 as well as by the finding of concomitant increases in conduction velocity and connexin expression in dibutyryl cAMP-treated cultured cardiac myocytes. 35 Although the precise in vivo relationship between absolute number of gap junctions and conduction velocity is not known, significant cardiac conduction defects are reported in heterozygotes for a connexin43 null mutation with an Ϸ50% reduction in gap junction content.…”

Section: Discussionmentioning

confidence: 95%

Downregulation of Immunodetectable Connexin43 and Decreased Gap Junction Size in the Pathogenesis of Chronic Hibernation in the Human Left Ventricle

et al. 1998

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Background-The regional wall motion impairment and predisposition to arrhythmias in human ventricular hibernation may plausibly result from abnormal intercellular propagation of the depolarizing wave front. This study investigated the hypothesis that altered patterns of expression of connexin43, the principal gap junctional protein responsible for passive conduction of the cardiac action potential, contribute to the pathogenesis of hibernation. Methods and Results-Patients with poor ventricular function and severe coronary artery disease underwent thallium scanning and MRI to predict regions of normally perfused, reversibly ischemic, or hibernating myocardium. Twenty-one patients went on to coronary artery bypass graft surgery, during which biopsies representative of each of the above classes were taken. Hibernation was confirmed by improvement in segmental wall motion at reassessment 6 months after surgery.

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Section: Discussionmentioning

confidence: 95%

Downregulation of Immunodetectable Connexin43 and Decreased Gap Junction Size in the Pathogenesis of Chronic Hibernation in the Human Left Ventricle

et al. 1998

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“…Gap junctions may play an important role in development by mediating the cell-to-cell transmission of signaling molecules involved in normal embryonic patterning . Connexin 43 (Cx43; Gja1 -Mouse Genome Informatics) is the predominant cardiac connexin subtype in the latter stages of embryogenesis and postnatally (Gros and Jongsma, 1996;Severs et al, 1996). Cx43 has been implicated in human developmental disorders (Paznekas et al, 2003), although its role in congenital cardiac disease is controversial (BritzCunningham et al, 1995;Casey and Ballabio, 1995;Debrus et al, 1997;Splitt et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube

Liu

Schneider

et al. 2006

Development

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Connexin 43 (Cx43) is expressed in the embryonic heart, cardiac neural crest (CNC) and neural tube, and germline knockout (KO) of Cx43 results in aberrant cardiac outflow tract (OFT) formation and abnormal coronary deployment. Prior studies suggest a vital role for CNC expression of Cx43 in heart development. Surprisingly, we found that conditional knockout (CKO) of Cx43 in the dorsal neural tube and CNC mediated by Wnt1-Cre failed to recapitulate the Cx43-null OFT phenotype, although coronary vasculature was abnormal in this mutant line. A broader CKO mediated by P3pro (Pax3)-Cre, involving both ventral and dorsal aspects of the thoracic neural tube and CNC, resulted in infundibular bulging and coronary anomalies similar to those seen in germline Cx43-null hearts. P3pro-Cre-mediated loss of Cx43 in the neural tube was characterized by a late phase of cellular delamination from the dorsal and lateral neural tube, a markedly increased abundance of neuroepithelium-derived cells outside of the neural tube and an excess of such cells infiltrating the heart and infundibulum. Thus, expression of Cx43 in the CNC is crucial for normal coronary deployment, but Cx43 is not required in the CNC for normal OFT morphogenesis. Rather, this study suggests a novel function for Cx43 in which Cx43 acts through non-crest neuroepithelial cells to suppress cellular delamination from the neural tube and thereby preserve normal OFT development.

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“…Considerable differences in phenotype exist between working myocytes and cells of the conduction system, including at the level of gene expression (Gorza et al, 1994;Thompson et al, 1995;Gros and Jongsma, 1996;Baker et al, 1997;Moorman et al, 1998;Gourdie et al, 1999;Kupershmidt et al, 1999). While it is now clear that working myocytes and conduction cells share common cellular progenitors in the chick Cheng et al, 1999), the transcription factors regulating the gene expression patterns that characterize divergent cardiomyogenic lineages remain poorly understood.…”

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confidence: 99%

Elevated expression of Nkx‐2.5 in developing myocardial conduction cells

et al. 2001

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A number of different phenotypes emerge from the mesoderm-derived cardiomyogenic cells of the embryonic tubular heart, including those comprising the cardiac conduction system. The transcriptional regulation of this phenotypic divergence within the cardiomyogenic lineage remains poorly characterized. A relationship between expression of the transcription factor Nkx-2.5 and patterning to form cardiogenic mesoderm subsequent to gastrulation is well established. Nkx-2.5 mRNA continues to be expressed in myocardium beyond the looped, tubular heart stage. To investigate the role of Nkx-2.5 in later development, we have determined the expression pattern of Nkx-2.5 mRNA by in situ hybridization in embryonic chick, fetal mouse, and human hearts, and of Nkx-2.5 protein by immunolocalization in the embryonic chick heart. As development progresses, significant nonuniformities emerge in Nkx-2.5 expression levels. Relative to surrounding forcegenerating ("working") myocardium, elevated Nkx-2.5 mRNA signal becomes apparent in the specialized cells of the conduction system. Similar differences are found in developing chick, human, and mouse fetal hearts, and nuclear-localized Nkx-2.5 protein is prominently expressed in differentiating chick conduction cells relative to adjacent working myocytes. This tissue-restricted expression of Nkx-2.5 is transient and correlates with the timing of spatio-temporal recruitment of cells to the central and the peripheral conduction system. Our data represent the first report of a transcription factor showing a stage-dependent restriction to different parts of the developing conduction system, and suggest some commonality in this development between birds and mammals. This dynamic pattern of expression is consistent with the hypothesis that Nkx-2.5, and its level of expression, have a role in regulation and/or maintenance of specialized fate selection by embryonic myocardial cells.

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Connexins in mammalian heart function

Cited by 268 publications

References 58 publications

Downregulation of Immunodetectable Connexin43 and Decreased Gap Junction Size in the Pathogenesis of Chronic Hibernation in the Human Left Ventricle

Downregulation of Immunodetectable Connexin43 and Decreased Gap Junction Size in the Pathogenesis of Chronic Hibernation in the Human Left Ventricle

Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube

Elevated expression of Nkx‐2.5 in developing myocardial conduction cells

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