A simple Markov model of sodium channels with a dynamic threshold

Characteristics of action potential generation are important to understanding brain functioning and, thus, must be understood and modeled. It is still an open question what model can describe concurrently the phenomena of sharp spike shape, the spike threshold variability, and the divisive effect of...

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Bibliographic Details
Published in:Journal of computational neuroscience 2014-08, Vol.37 (1), p.181-191
Main Authors: Chizhov, A. V., Smirnova, E. Yu, Kim, K. Kh, Zaitsev, A. V.
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Animals, Newborn
Biomedical and Life Sciences
Biomedicine
Biophysics
Cerebral Cortex - cytology
Electric Stimulation
Human Genetics
In Vitro Techniques
Male
Markov Chains
Models, Neurological
Nerve Net - physiology
Neurology
Neurosciences
Nonlinear Dynamics
Patch-Clamp Techniques
Pyramidal Cells - physiology
Rats
Rats, Wistar
Sodium Channels - physiology
Theory of Computation
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Summary:Characteristics of action potential generation are important to understanding brain functioning and, thus, must be understood and modeled. It is still an open question what model can describe concurrently the phenomena of sharp spike shape, the spike threshold variability, and the divisive effect of shunting on the gain of frequency-current dependence. We reproduced these three effects experimentally by patch-clamp recordings in cortical slices, but we failed to simulate them by any of 11 known neuron models, including one- and multi-compartment, with Hodgkin-Huxley and Markov equation-based sodium channel approximations, and those taking into account sodium channel subtype heterogeneity. Basing on our voltage-clamp data characterizing the dependence of sodium channel activation threshold on history of depolarization, we propose a 3-state Markov model with a closed-to-open state transition threshold dependent on slow inactivation. This model reproduces the all three phenomena. As a reduction of this model, a leaky integrate-and-fire model with a dynamic threshold also shows the effect of gain reduction by shunt. These results argue for the mechanism of gain reduction through threshold dynamics determined by the slow inactivation of sodium channels.
ISSN:0929-5313
1573-6873
DOI:10.1007/s10827-014-0496-6