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Functional differences between human Cx37 polymorphic hemichannels

Desplantez, Thomas
Wong, Cindy W.
Roth, Isabelle
Weingart, Robert
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/metabolismCell AdhesionConnexins/*genetics/*metabolismElectrophysiological PhenomenaGap Junctions/*metabolismHeLa CellsHumans*Polymorphism, GeneticTransfection
PMID: 19166859
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Research group L'athérosclérose (665)
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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

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Deposited on : 2012-04-23

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