title: The influence of gap junction network complexity on pulmonary artery smooth muscle reactivity in normoxic and chronically hypoxic conditions.
abstract: Experiments on intrapulmonary arteries (IPAs) isolated from rats maintained in normoxia and chronic hypobaric hypoxia showed that in normoxia, the IPA contractile sensitivity to KCl was not modified by gap junction inhibition. In contrast, chronic hypoxia induced an endothelium-independent hypersensitivity, which was suppressed by gap junction inhibition. For the theoretical analysis of these results, we developed a model of interconnected myocytes. Given that smooth muscle cells in IPAs are known to communicate via gap junctions, we regard the cytoarchitecture of the IPA as a spatial network, in which nodes represent individual smooth muscle cells and the links signify intercellular communication. A single-cell model that drives the dynamics of individual nodes includes the major elements of voltage-dependent Ca(2+) signalling. In addition, interindividual variability of SMCs is introduced by distributing the reversal potentials for K(+). Cell-to-cell connection consists of passive Ca(2+) diffusion and electrical coupling, and connection between cells is determined by the topology of the intercellular network. Model predictions indicate that the experimental results can be explained by topological modifications and not by changes in the number of gap junctions. According to the model, in normoxia the myocytes are connected in a complex network, whereas chronic hypoxia is related to loss of complexity, leading to hypersensitivity. Our results thus indicate that chronic hypoxia entails gap junction network rearrangements, leading to disturbances in the intercellular communication pathways.
authors.affiliation: M. Gosak: University of Maribor, Department of Physics, Faculty of Natural Sciences and Mathematics, Koroška cesta 160, SI-2000 Maribor, Slovenia. marko.gosak@uni-mb.si.
authors.forename: Marko
authors.initials: M
authors.lastname: Gosak
authors.forename: Christelle
authors.initials: C
authors.lastname: Guibert
authors.forename: Marie
authors.initials: M
authors.lastname: Billaud
authors.forename: Etienne
authors.initials: E
authors.lastname: Roux
authors.forename: Marko
authors.initials: M
authors.lastname: Marhl
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D032342:Muscle Cells / Q000378:metabolism / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011188:Potassium; D002118:Calcium