Biological mechanism and identifiability of a class of stationary conductance model for Voltage-gated Ion channels

TL;DR

This paper introduces a thermodynamics-based approach to determine the minimal number of states needed in Markov models for voltage-gated ion channels, ensuring model identifiability and better alignment with experimental data.

Contribution

It proposes a novel thermodynamics-inspired method to define stationary conductance, establishing a lower bound on model complexity and ensuring parameter identifiability.

Findings

Model matches published current-voltage data

Parameters are identifiable from standard experiments

Provides a thermodynamics-based minimal state count

Abstract

The physiology of voltage gated ion channels is complex and insights into their gating mechanism is incomplete. Their function is best represented by Markov models with relatively large number of distinct states that are connected by thermodynamically feasible transitions. On the other hand, popular models such as the one of Hodgkin and Huxley have empirical assumptions that are generally unrealistic. Experimental protocols often dictate the number of states in proposed Markov models, thus creating disagreements between various observations on the same channel. Here we aim to propose a limit to the minimum number of states required to model ion channels by employing a paradigm to define stationary conductance in a class of ion-channels. A simple expression is generated using concepts in elementary thermodynamics applied to protein conformational transitions. Further, it matches well many published channel current-voltage characteristics and parameters of the model are found to be identifiable and easily determined from usual experimental protocols.