Application of stochastic automata networks for creation of continuous time Markov chain models of voltage gating of gap junction channels.

Mindaugas Snipas,Osvaldas Pranevicius,Nerijus Paulauskas,Feliksas F Bukauskas,Henrikas Pranevicius,Mindaugas Pranevicius

doi:10.1155/2015/936295

Abstract

The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC) of voltage gating of gap junction (GJ) channels composed of connexin protein. This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs), which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure. All of that allowed us to develop efficient numerical methods for a steady-state solution of CTMC models. This allowed us to accelerate CPU time, which is necessary to solve CTMC models, ∼20 times.

Highlights

Gap-junctional communication plays an important role in many processes, such as impulse propagation in the heart, communication between neurons and glia, organ formation during early development, regulation of cell proliferation, and metabolic exchange between cells of various tissues, including the lens that lack blood circulation
The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC) of voltage gating of gap junction (GJ) channels composed of connexin protein
This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs), which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure

Summary

Introduction

Gap-junctional communication plays an important role in many processes, such as impulse propagation in the heart, communication between neurons and glia, organ formation during early development, regulation of cell proliferation, and metabolic exchange between cells of various tissues, including the lens that lack blood circulation. Gap junction (GJ) channels are formed of connexin (Cx) proteins, which belong to a family of integral membrane proteins exhibiting a tissue specific expression pattern. GJs provide a direct pathway for electrical and metabolic signalling between the cells [1]. Twenty-one isoforms of Cxs form GJ channels [2]. Each GJ channel is composed of two hemichannels (HCs), both oligomerized of six Cxs. Cxs have four alpha helical transmembrane domains (M1 to M4), intracellular N- and

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Conclusion