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Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive
Connexins (Cx) form gap junctions and allow the coordination of cellular behaviour. In vessels, expression of Cx40, Cx37, and Cx43 is well established and specifically Cx40 serves important functions in endothelial cells. In contrast, expression and physiological functions of Cx45 is unclear althoug...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407082/ https://www.ncbi.nlm.nih.gov/pubmed/22848755 http://dx.doi.org/10.1371/journal.pone.0042287 |
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author | Schmidt, Volker J. Jobs, Alexander von Maltzahn, Julia Wörsdörfer, Philipp Willecke, Klaus de Wit, Cor |
author_facet | Schmidt, Volker J. Jobs, Alexander von Maltzahn, Julia Wörsdörfer, Philipp Willecke, Klaus de Wit, Cor |
author_sort | Schmidt, Volker J. |
collection | PubMed |
description | Connexins (Cx) form gap junctions and allow the coordination of cellular behaviour. In vessels, expression of Cx40, Cx37, and Cx43 is well established and specifically Cx40 serves important functions in endothelial cells. In contrast, expression and physiological functions of Cx45 is unclear although its expression has been suggested in vascular smooth muscle (VSM). Therefore, we studied expression and function of Cx45 in vessels using different mice models allowing to identify and delete Cx45. Smooth muscle cell (SMC)-specific deletion was achieved by the Cre/loxP system using Cre-recombinase driven by a Nestin promoter. Deletion of Cx45 leads concomitantly to the expression of enhanced green fluorescence protein (EGFP) in these mice. Conduction of vasomotor responses was studied in cremasteric arterioles using intravital microscopy and arterial pressure was measured telemetrically. Cx45 is transcriptionally expressed in VSM as detected by EGFP expression in SMC-specific Cx45-deficient mice (Cx45fl/fl:Nestin-Cre) but not in endothelial cells (Cx45fl/fl:TIE2-Cre). Moreover, EGFP was located at VSM cell borders in arterioles of transgenic mice carrying an EGFP-tagged Cx45. Expectedly, arteriolar conduction of dilations evoked by the endothelium-dependent agonist acetylcholine were not different between Cx45fl/fl:Nestin-Cre mice and controls carrying homozygously a floxed Cx45 gene (Cx45fl/fl). Surprisingly, the amplitude of locally initiated endothelium-independent constrictions (K(+)) and dilations (adenosine) declined similarly with distance in both genotypes indicating an intact VSM conduction pathway also in mice being deficient for Cx45 in VSM. Arterial pressure was not different between freely moving Cx45fl/fl and Cx45fl/fl:Nestin-Cre mice during day or night. We conclude that Cx45 is physiologically expressed in VSM, but not in EC in murine arterioles. However, Cx45 is dispensable for the conduction of vasomotor responses along these arterioles. Possibly, other Cx functionally replace the lack of Cx45 in VSM. The reported role of Cx45 in renin secretion does not seem to alter arterial pressure in freely moving mice. |
format | Online Article Text |
id | pubmed-3407082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34070822012-07-30 Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive Schmidt, Volker J. Jobs, Alexander von Maltzahn, Julia Wörsdörfer, Philipp Willecke, Klaus de Wit, Cor PLoS One Research Article Connexins (Cx) form gap junctions and allow the coordination of cellular behaviour. In vessels, expression of Cx40, Cx37, and Cx43 is well established and specifically Cx40 serves important functions in endothelial cells. In contrast, expression and physiological functions of Cx45 is unclear although its expression has been suggested in vascular smooth muscle (VSM). Therefore, we studied expression and function of Cx45 in vessels using different mice models allowing to identify and delete Cx45. Smooth muscle cell (SMC)-specific deletion was achieved by the Cre/loxP system using Cre-recombinase driven by a Nestin promoter. Deletion of Cx45 leads concomitantly to the expression of enhanced green fluorescence protein (EGFP) in these mice. Conduction of vasomotor responses was studied in cremasteric arterioles using intravital microscopy and arterial pressure was measured telemetrically. Cx45 is transcriptionally expressed in VSM as detected by EGFP expression in SMC-specific Cx45-deficient mice (Cx45fl/fl:Nestin-Cre) but not in endothelial cells (Cx45fl/fl:TIE2-Cre). Moreover, EGFP was located at VSM cell borders in arterioles of transgenic mice carrying an EGFP-tagged Cx45. Expectedly, arteriolar conduction of dilations evoked by the endothelium-dependent agonist acetylcholine were not different between Cx45fl/fl:Nestin-Cre mice and controls carrying homozygously a floxed Cx45 gene (Cx45fl/fl). Surprisingly, the amplitude of locally initiated endothelium-independent constrictions (K(+)) and dilations (adenosine) declined similarly with distance in both genotypes indicating an intact VSM conduction pathway also in mice being deficient for Cx45 in VSM. Arterial pressure was not different between freely moving Cx45fl/fl and Cx45fl/fl:Nestin-Cre mice during day or night. We conclude that Cx45 is physiologically expressed in VSM, but not in EC in murine arterioles. However, Cx45 is dispensable for the conduction of vasomotor responses along these arterioles. Possibly, other Cx functionally replace the lack of Cx45 in VSM. The reported role of Cx45 in renin secretion does not seem to alter arterial pressure in freely moving mice. Public Library of Science 2012-07-27 /pmc/articles/PMC3407082/ /pubmed/22848755 http://dx.doi.org/10.1371/journal.pone.0042287 Text en © 2012 Schmidt et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Schmidt, Volker J. Jobs, Alexander von Maltzahn, Julia Wörsdörfer, Philipp Willecke, Klaus de Wit, Cor Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive |
title | Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive |
title_full | Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive |
title_fullStr | Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive |
title_full_unstemmed | Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive |
title_short | Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive |
title_sort | connexin45 is expressed in vascular smooth muscle but its function remains elusive |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407082/ https://www.ncbi.nlm.nih.gov/pubmed/22848755 http://dx.doi.org/10.1371/journal.pone.0042287 |
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