title: Connexins and M3 muscarinic receptors contribute to heterogeneous Ca(2+) signaling in mouse aortic endothelium.
abstract: OBJECTIVE
  Smooth muscle tone is controlled by Ca(2+) signaling in the endothelial layer. Mouse endothelial cells are interconnected by gap junctions made of Connexin40 (Cx40) and Cx37, which allow the exchange of signaling molecules to coordinate their activity. Here, we investigated the role of Cx40 in the endothelial Ca(2+) signaling of the mouse aorta.
  
  
  METHODS
  Ca(2+) imaging was performed on intact aortic endothelium from both wild type (Cx40+/+) and Connexin40-deficient (Cx40 -/-) mice.
  
  
  RESULTS
  Acetylcholine (ACh) induced early fast and high amplitude Ca(2+) transients in a fraction of endothelial cells expressing the M3 muscarinic receptors. Inhibition of intercellular communication using carbenoxolone or octanol fully blocked the propagation of ACh-induced Ca(2+) transients toward adjacent cells in WT and Cx40-/- mice. As compared to WT, Cx40-/- mice displayed a reduced propagation of ACh-induced Ca(2+) waves, indicating that Cx40 contributes to the spreading of Ca(2+) signals. The propagation of those Ca(2+) responses was not blocked by suramin, a blocker of purinergic ATP receptors, indicating that there is no paracrine effect of ATP release on the Ca(2+) waves.
  
  
  CONCLUSIONS
  Altogether our data show that Cx40 and Cx37 contribute to the propagation and amplification of the Ca(2+) signaling triggered by ACh in endothelial cells expressing the M3 muscarinic receptors.
authors: Department of Zoology and Animal Biology, Laboratory of Vascular Cell Physiology, University of Geneva, Geneva 4, Switzerland.
authors: François-Xavier
authors: FX
authors: Boittin
authors: Florian
authors: F
authors: Alonso
authors: Loïc
authors: L
authors: Le Gal
authors: Florent
authors: F
authors: Allagnat
authors: Jean-Louis
authors: JL
authors: Bény
authors: Jacques-Antoine
authors: JA
authors: Haefliger
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000442:Octanols / Q000494:pharmacology; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D000109:Acetylcholine; D000255:Adenosine Triphosphate; D000897:Anti-Ulcer Agents; D002118:Calcium; D002229:Carbenoxolone; D017630:Connexins; D000442:Octanols; D043587:Receptor, Muscarinic M3; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein