Pharmacological modulation and differential regulation of the cardiac gap junction proteins connexin 43 and connexin 40

Détails

ID Serval
serval:BIB_21BAA828EE52
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Pharmacological modulation and differential regulation of the cardiac gap junction proteins connexin 43 and connexin 40
Périodique
Biologie Cellulaire
Auteur(s)
Dhein  S., Polontchouk  L., Salameh  A., Haefliger  J. A.
ISSN
0248-4900 (Print)
Statut éditorial
Publié
Date de publication
11/2002
Volume
94
Numéro
7-8
Pages
409-22
Notes
Journal Article
Review --- Old month value: Nov
Résumé
Gap junction channels provide the basis for the electrical syncytial properties of the heart as a communicating electrical network. Cardiac gap junction channels are predominantly composed of connexin 40 or connexin 43. The conductance of these channels (g(j)) can be regulated pharmacologically: substances which activate protein kinase C, protein kinase A or protein kinase G may alter Cx43 gap junction conductance. However, for PKC, this seems to be subtype specific. Thus, antiarrhythmic peptides can enhance g(j) via activation of PKCepsilon, while FGF-2 reduces g(j) via PKCepsilon. Lipophilic drugs can uncouple the channels. Besides an acute regulation of g(j), the expression of the cardiac connexins can also be regulated. A decrease in Cx43 with a concomitant increase in Cx40 has been found in end-stage failing hearts, while in renovascular hypertension, an increase in Cx43 has been described. Mediators like endothelin-1, angiotensin-II, TGF-beta, VEGF, and cAMP have been shown to increase Cx43. Interestingly, endothelin-1 and angiotensin-II increased Cx43 but did not affect Cx40 expression. In contrast, in humans suffering from atrial fibrillation (AF), the content in Cx40 can be enhanced while Cx43 was unaltered, although in several other studies, other changes of the cardiac connexins were found, which might be related to the type of AF. Regarding the role of calcium, the content in both Cx40 and Cx43 was decreased in cultured neonatal rat cardiomyocytes after 24 h administration of 100 nM verapamil. Thus, gap junctional channels can be affected pharmacologically either acutely by modulating gap junction conductance or chronically by altering gap junction protein expression. Interestingly, it appears that the expression of Cx43 and Cx40 can be differentially regulated.
Mots-clé
Animals Connexin 43/biosynthesis/*drug effects/physiology Connexins/biosynthesis/*drug effects/physiology Electric Conductivity Gene Expression Regulation/*drug effects/physiology Humans Myocardium/chemistry/pathology Signal Transduction/drug effects/physiology
Pubmed
Web of science
Création de la notice
25/01/2008 14:48
Dernière modification de la notice
20/08/2019 13:58
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