Determination of rate kinetics in ion channels by the path probability method and Onsager reciprocity theorem

In this study, we propose a theoretical framework for the determination of rate kinetics in the ion channels. In this framework, we firstly formulate the kinetic equation for the time-dependent open-state probability of the gate and forward and backward rate kinetics based on the path probability method with three parameters, explicitly. Then, we construct a tool to determine if fitted rate kinetics satisfy the experimental data by deriving kinetic coefficients of activation and inactivation gates based on the Onsager reciprocity theorem. The proposed framework is based on the principles of statistical physics and conceptually quite different from those of conventional models. We also illustrate its applicability based on the empirical inactivation kinetics of T-type calcium channel from thalamic relay neurons, and then compare it with the linear and nonlinear thermodynamic models for the same calcium channel. The results of the present study indicate that our methodology suggests a general framework for the determination of rate kinetics in ion channels.