Phenomenological models of NaV1.5. A side by side, procedural, hands-on comparison between Hodgkin-Huxley and kinetic formalisms

Background Computational models of ionic channels represent the building blocks of conductance-based, biologically inspired models of neurons and neural networks. Ionic channels are still widely modelled by means of the formalism developed by the seminal work of Hodgkin and Huxley, although the electrophysiological features of the channels are currently known to be better fitted by means of kinetic (Markov-type) models. Objective The present study is aimed at showing why kinetic, simplified models are better suited to model ionic channels compared to Hodgkin and Huxley models, and how the manual optimization process is rationally carried out in practice for these two kinds of models. Methods Previously published experimental data on macroscopic currents of an illustrative ionic channel (NaV1.5) are exploited to develop a step by step optimization of the two models in close comparison. The proposed kinetic model is a simplified one, consisting of five states and ten transitions. Results A conflicting practical limitation is recognized for the Hodgkin and Huxley model, which only supplies one parameter to model two distinct electrophysiological behaviours (namely the steady-state availability and the recovery from inactivation). In addition, a step by step procedure is provided to correctly optimize the kinetic model. Conclusion Simplified kinetic models are at the moment the best option to closely approximate the known complexity of the ionic channel macroscopic currents. Their optimization is achievable by means of a rationally guided procedure, and it results in models with computational burdens comparable with those from Hodgkin and Huxley models.

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