Intercellular calcium waves in primary cultured rat mesenteric smooth muscle cells are mediated by Connexin43

Halidi, Nadia; Alonso, Florian; Burt, Janis M.; Bény, Jean‐Louis; Haefliger, Jacques‐Antoine; Meister, Jean-Jacques

doi:10.3109/15419061.2012.690792

Cited by 12 publications

(11 citation statements)

References 42 publications

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“…The fact that gap-junctional communication is required for contractile wave propagation/generation is consistent with previous work on Ca 2þ communication in smooth muscle cell cultures [14,32] and adult gut motility [33]. Other small molecules that diffuse through gap junctions, like ATP, may play a role in the propagation of the calcium wave [31,34].…”

Section: Discussionsupporting

confidence: 89%

The first digestive movements in the embryo are mediated by mechanosensitive smooth muscle calcium waves

Chevalier¹

2018

Phil. Trans. R. Soc. B

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Peristalsis enables transport of the food bolus in the gut. Here, I show by dynamic ex-vivo intra-cellular calcium imaging on living embryonic gut transverse sections that the most primitive form of peristalsis that occurs in the embryo is the result of inter-cellular, gapjunction dependent calcium waves that propagate in the circular smooth muscle layer. I show that the embryonic gut is an intrinsically mechanosensitive organ, as the slightest externally applied mechanical stimulus triggers contractile waves. This dynamic response is an embryonic precursor of the "law of the intestine" (peristaltic reflex). I show how characteristic features of early peristalsis such as counterpropagating wave annihilation, mechanosensitivity and nucleation after wounding all result from known properties of calcium waves. I finally demonstrate that inter-cellular mechanical tension does not play a role in the propagation mechanism of gut contractile waves, unlike what has been recently shown for the embryonic heartbeat. Calcium waves are an ubiquitous dynamic signaling mechanism in biology: here I show that they are the foundation of digestive movements in the developing embryo.

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Section: Discussionsupporting

confidence: 89%

The first digestive movements in the embryo are mediated by mechanosensitive smooth muscle calcium waves

Chevalier¹

2018

Phil. Trans. R. Soc. B

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“…Previous studies confirmed that intracellular Ca 2+ concentration regulates the permeability of gap junctions composed of Cx43 (39,40). Increased abundance of intracellular Ca 2+ can activate calcium-dependent proteolytic enzymes (calpains), which can degrade a variety of proteins, and change cell structure and function (41).…”

Section: Discussionmentioning

confidence: 87%

Protective effect of diltiazem on myocardial ischemic rats induced by isoproterenol

2017

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The aim of the present study was to analyze the effect of diltiazem on myocardial fibrosis and remodeling of connexin43 (Cx43) in myocardial ischemic rats and mechanisms underlying these processes. A total of 36 Sprague‑Dawley rats were randomly allocated into three groups (control, isoproterenol and isoproterenol with diltiazem). The myocardial ischemic model was established by 5 mg/kg/day isoproterenol administration for 7 days, and the diltiazem group received 25 mg/kg/day diltiazem for 4 weeks. Following the treatment, paraffin sections were prepared to observe microstructural changes and to evaluate the concentration of Ca2+ in myocardium. The expression of transforming growth factors‑β1 (TGF‑β1), mothers against decapentaplegic homologues (Smad)2 and 7 and Cx43, were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. The percentage Cx43 expression in intercalated disks was evaluated using immunohistochemistry. Fibrosis did not differ significantly between the control and the diltiazem‑treated group. The concentration of Ca2+ increased in the myocardium of model rats. The expression of Smad7 and Cx43 was decreased in the rat model, while the expression of TGF‑β1 and Smad2 was increased. There was a significant decrease in the relative abundance of intercalated disk Cx43 in the model group. The results of the present study suggest that diltiazem may serve a protective role during remodeling of myocardial ischemia, especially in fibrosis and Cx43 remodeling.

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“…The potential vasculoprotective effect of Cx43 blockade was then tested in human saphenous vein, using the pan-Cx inhibitor carbenoxolone (100 μM) or the specific Cx43 inhibiting peptide 43 Gap26 (200 μM) [ 30 , 31 ]. Both strategies reduced the development of IH ( Fig 10 ) and myointimal proliferation (PCNA staining) ( Fig 10 ) observed after 10 days of static culture, suggesting that Cx43 is the main Cx involved in VSMC proliferation and IH.…”

Section: Resultsmentioning

confidence: 99%

Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

et al. 2015

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Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide 43gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment.

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Intercellular calcium waves in primary cultured rat mesenteric smooth muscle cells are mediated by Connexin43

Cited by 12 publications

References 42 publications

The first digestive movements in the embryo are mediated by mechanosensitive smooth muscle calcium waves

The first digestive movements in the embryo are mediated by mechanosensitive smooth muscle calcium waves

Protective effect of diltiazem on myocardial ischemic rats induced by isoproterenol

Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

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