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The influence of gap junction network complexity on pulmonary artery smooth muscle reactivity in normoxic and chronically hypoxic conditions
Author(s) -
Gosak Marko,
Guibert Christelle,
Billaud Marie,
Roux Etienne,
Marhl Marko
Publication year - 2014
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2013.074971
Subject(s) - gap junction , hypoxia (environmental) , myocyte , pulmonary artery , intracellular , neuroscience , biology , chemistry , medicine , microbiology and biotechnology , oxygen , organic chemistry
New Findings• What is the central question of this study? Experimental results on intrapulmonary arteries indicate that the relationship between gap junctional intercellular communication and its functional involvement in tissue reactivity is very complex, both in normoxic and in chronically hypoxic conditions. The relationship between the gap junction network and vasoreactivity is poorly known and needs to be explored, including theoretical modelling approaches. • What is the main finding and its importance? Our results indicate that the role of gap junctions and their contribution to intrapulmonary artery reactivity depends crucially on the topology of the gap junctional communication network. In normoxia, myocytes are connected in a complex network, whereas chronic hypoxia is related to loss of the network complexity, leading to hypersensitivity.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.