Nonlinear thermodynamic models of voltage-dependent currents.
Alain Destexhe and John R. Huguenard
Journal of Computational Neuroscience 9: 259-270, 2000.
Abstract:
Hodgkin and Huxley provided the first quantitative description of
voltage-dependent currents and adjusted their model to experimental data using
empirical functions of voltage. A physically-plausible formalism was proposed
later by assuming that transition rates depend exponentially on a free-energy
barrier, by analogy with the theory of reaction rates. It was also assumed that
the free-energy depends linearly on voltage. This thermodynamic formalism can
accurately describe many processes, but the resulting time constants can be
arbitrarily fast, which may also lead to aberrant behavior. We considered here a
physically plausible solution to this problem by including nonlinear effects of
the electrical field on the free-energy. We show that including effects such as
mechanical constraints, inherent to the structure of the ion channel protein,
leads to more accurate thermodynamic models. These models can account for
voltage-dependent transitions which are rate-limited in a given voltage range,
without invoking additional states. We illustrate their applicability to fit
experimental data by considering the case of the T-type calcium current in
thalamic neurons.
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