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Functional differences between human Cx37 polymorphic hemichannels
|Published in||Journal of Molecular and Cellular Cardiology. 2009, vol. 46, no. 4, p. 499-507|
|Abstract||A polymorphism in the human Cx37 gene (C1019T), resulting in a non-conservative amino acid change in the regulatory C-terminus of the Cx37 protein (P319S), has been proposed as a prognostic marker for atherosclerosis. We have recently demonstrated that Cx37 hemichannels control the initiation of atherosclerotic plaque development by regulating ATP-dependent monocyte adhesion in atherosclerosis-susceptible apolipoprotein E-deficient mice. In this study, we have measured the electrical properties of Cx37 hemichannels (HCs) and gap junction channels (GJCs) with voltage-clamp methods. To this end, we have transfected hCx37-P319, hCx37-S319 or empty pIRES-eGFP vector cDNA into communication-deficient HeLa cells. In clones expressing similar levels of Cx37, exposure of single cells to low-Ca(2+) solution induced a voltage-sensitive HC current. The analysis yielded a bell-shaped function g(hc)=f(V(m)) (g(hc): normalized conductance at steady state; V(m): membrane potential) with a maximum around V(m)=-30 mV. The peak g(hc) of Cx37-P319 was 3-fold larger than that of Cx37-S319 HCs. Experiments on cell pairs revealed that Cx37-P319 GJCs exhibited a 1.5-fold larger unitary conductance than Cx37-S319 GJCs. Hence, the larger peak g(hc) of the former may reflect a larger conductance of their HCs. Using the same clones, we found that Cx37-P319 cells released more ATP and were less adhesive than Cx37-S319 cells. The reduction in adhesiveness of Cx37-expressing cells was prevented by extracellular apyrase. We conclude that the differences in biophysical properties between polymorphic HCs may be responsible for inequality in ATP release between Cx37-P319 and Cx37-S319 cells, which results in differential cell adhesion.|
|Keywords||Adenosine Triphosphate/metabolism — Cell Adhesion — Connexins/*genetics/*metabolism — Electrophysiological Phenomena — Gap Junctions/*metabolism — HeLa Cells — Humans — *Polymorphism, Genetic — Transfection|
|Research group||L'athérosclérose (665)|
|DEROUETTE, Jean-Paul et al. Functional differences between human Cx37 polymorphic hemichannels. In: Journal of Molecular and Cellular Cardiology, 2009, vol. 46, n° 4, p. 499-507. doi: 10.1016/j.yjmcc.2008.12.018 https://archive-ouverte.unige.ch/unige:19771|