Stochastic models and simulation of ion channel dynamics

The behaviour of ion channels within cardiac and neuronal cells is intrinsically stochastic in nature. When the number of channels is small this stochastic noise is large and can have an impact on the dynamics of the system which is potentially an issue when modelling small neurons and drug block in cardiac cells. While exact methods correctly capture the stochastic dynamics of a system they are computationally expensive, restricting their inclusion into tissue level models and so approximations to exact methods are often used instead. The other issue in modelling ion channel dynamics is that the transition rates are voltage dependent, adding a level of complexity as the channel dynamics are coupled to the membrane potential. By assuming that such transition rates are constant over each time step, it is possible to derive a stochastic differential equation (SDE), in the same manner as for biochemical reaction networks, that describes the stochastic dynamics of ion channels. While such a model is more computationally efficient than exact methods we show that there are analytical problems with the resulting SDE as well as issues in using current numerical schemes to solve such an equation. We therefore make two contributions: develop a different model to describe the stochastic ion channel dynamics that analytically behaves in the correct manner and also discuss numerical methods that preserve the analytical properties of the model.

[1]  M. Günther,et al.  Positive numerical integration of Stochastic Differential Equations , 2004 .

[2]  Huxley Af,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve. 1952. , 1990 .

[3]  Olli Yli-Harja,et al.  Modeling single neuron behavior using stochastic differential equations , 2006, Neurocomputing.

[4]  Christian Kahl,et al.  Fast strong approximation Monte Carlo schemes for stochastic volatility models , 2006 .

[5]  S. J. Malham,et al.  Positive and implicit stochastic volatility simulation , 2008 .

[6]  M. Arita,et al.  Late Sodium Current and Its Contribution to Action Potential Configuration in Guinea Pig Ventricular Myocytes , 1989, Circulation research.

[7]  Jürgen Pahle,et al.  Biochemical simulations: stochastic, approximate stochastic and hybrid approaches , 2008, Briefings Bioinform..

[8]  D. Snyders,et al.  High affinity open channel block by dofetilide of HERG expressed in a human cell line. , 1996, Molecular pharmacology.

[9]  P. Kloeden,et al.  Numerical Solution of Stochastic Differential Equations , 1992 .

[10]  D. Dijk,et al.  A comparison of biased simulation schemes for stochastic volatility models , 2008 .

[11]  Stefano M. Iacus,et al.  Simulation and Inference for Stochastic Differential Equations: With R Examples , 2008 .

[12]  K. Zygalakis,et al.  Fast stochastic simulation of biochemical reaction systems by alternative formulations of the chemical Langevin equation. , 2010, The Journal of chemical physics.

[13]  Tianhai Tian,et al.  A multi-scaled approach for simulating chemical reaction systems. , 2004, Progress in biophysics and molecular biology.

[14]  Y. Rudy,et al.  Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia , 1999, Nature.

[15]  S. Dvinskikh,et al.  Heteronuclear dipolar recoupling in solid-state nuclear magnetic resonance by amplitude-, phase-, and frequency-modulated Lee-Goldburg cross-polarization. , 2005, The Journal of chemical physics.

[16]  Leif Andersen Simple and efficient simulation of the Heston stochastic volatility model , 2008 .

[17]  Yoram Rudy,et al.  Computational biology in the study of cardiac ion channels and cell electrophysiology , 2006, Quarterly Reviews of Biophysics.

[18]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1990 .

[19]  D. Gillespie The chemical Langevin equation , 2000 .

[20]  S. Ninomiya,et al.  Weak Approximation of Stochastic Differential Equations and Application to Derivative Pricing , 2006, math/0605361.

[21]  Esteban Moro Egido,et al.  Boundary Preserving Semianalytic Numerical Algorithms for Stochastic Differential Equations , 2007, SIAM J. Sci. Comput..

[22]  S. Basov Simulation and Inference for Stochastic Differential Equations: With R Examples , 2010 .

[23]  Yoram Rudy,et al.  Pharmacogenetics and anti-arrhythmic drug therapy: a theoretical investigation. , 2007, American journal of physiology. Heart and circulatory physiology.

[24]  T. McMillen Simulation and Inference for Stochastic Differential Equations: With R Examples , 2008 .

[25]  S. Ross,et al.  A theory of the term structure of interest rates'', Econometrica 53, 385-407 , 1985 .

[26]  Aurélien Alfonsi,et al.  High order discretization schemes for the CIR process: Application to affine term structure and Heston models , 2010, Math. Comput..

[27]  D. Gillespie Exact Stochastic Simulation of Coupled Chemical Reactions , 1977 .

[28]  Vigirdas Mackevicius,et al.  On weak approximations of CIR equation with high volatility , 2010, Math. Comput. Simul..

[29]  W. Ewens Mathematical Population Genetics , 1980 .

[30]  Yiannis Kaznessis,et al.  Accurate hybrid stochastic simulation of a system of coupled chemical or biochemical reactions. , 2005, The Journal of chemical physics.

[31]  D. Gillespie A rigorous derivation of the chemical master equation , 1992 .

[32]  W. Feller TWO SINGULAR DIFFUSION PROBLEMS , 1951 .

[33]  Thomas A. Henzinger,et al.  Hybrid numerical solution of the chemical master equation , 2010, CMSB '10.

[34]  Fox,et al.  Emergent collective behavior in large numbers of globally coupled independently stochastic ion channels. , 1994, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[35]  S. Karlin,et al.  A second course in stochastic processes , 1981 .

[36]  D. Gillespie The Chemical Langevin and Fokker−Planck Equations for the Reversible Isomerization Reaction† , 2002 .