Effects of non-linear GJ channels on the AP propagation : a modelling insight

Anđela Davidović 1, 2, 3, 4 Yves Coudière 4, 1, 2, 3 Thomas Desplantez 4, 3 Clair Poignard 5, 2
1 CARMEN - Modélisation et calculs pour l'électrophysiologie cardiaque
IMB - Institut de Mathématiques de Bordeaux, Inria Bordeaux - Sud-Ouest, IHU-LIRYC
5 MONC - Modélisation Mathématique pour l'Oncologie
IMB - Institut de Mathématiques de Bordeaux, Inria Bordeaux - Sud-Ouest, Institut Bergonié - CRLCC Bordeaux
Abstract : Background: Velocity and pattern of propagation of cardiac AP depends on structural and functional properties of the tissue, such as conductivity, dynamics of transmembrane ionic channels and gap junctions (GJ). Gap junctions are clusters of channels that connect adjacent cells. A gap junction channel (GJC) is made of proteins named ­ connexins. Electrical behavior of GJCs depend on the type and arrangement of their connexin composition. The dominating connexins in cardiac myocytes are Cx43, Cx45 and Cx40. Methods and results: In current mathematical models, GJCs are considered to be passive. But, the experimental results, obtained by the dual­voltage clamp technique, show that GJCs display biophysical electrical properties such as voltage gating, i.e. a time and voltage dependence. Here we model Cx43 GJCs. We use the Hodgkin­Huxley formalism to describe GJCs conductance via one gating variable g j = g j (t, V j ). From our experimental results we obtain model parameters: the normalised steady state conductance and the time constant to reach the steady state, both voltage dependent. Once we have described the behavior of the single GJC, we write the mathematical model of the tissue, where we apply GJ current on specific parts of the cells’ membranes. Numerics and outlook: Some 3D numerical experiments are currently being performed on a thin strip of cells, in order to compare the model’s results with the experimental ones. We use a monolayer of 50 × 3 cells, represented by cylinders of 100μm length and 10μm radius, with 2μm inter­cellular distance. We model GJCs on the cross sections of the cylinders. Finally, we apply an external stimulus on the border of the domain, and observe the propagation of the AP. Our goal is to make a mathematical model of the heterogeneous GJCs, including Cx45 channels, as these have been shown to play a role in arrythmogenesis.
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Poster
33RD ANNUAL MEETING OF THE EUROPEAN SECTION OF THE ISHR , Jul 2015, Bordeaux, France
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Contributeur : Andjela Davidovic <>
Soumis le : mardi 20 décembre 2016 - 11:51:56
Dernière modification le : mardi 1 mai 2018 - 18:50:03

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Anđela Davidović, Yves Coudière, Thomas Desplantez, Clair Poignard. Effects of non-linear GJ channels on the AP propagation : a modelling insight. 33RD ANNUAL MEETING OF THE EUROPEAN SECTION OF THE ISHR , Jul 2015, Bordeaux, France. 〈hal-01418687〉

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