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Mahmut Ozer

Publications and source records attributed to Mahmut Ozer.

6 recordsLinked to original sources

A comparative tool for the validity of rate kinetics in ion channels by Onsager reciprocity theorem.

The precise form of the rate constant functions of ion channels is very crucial for reproducing the electrophysiological behavior. Therefore, how well they account for experimental data plays an important role in the behavior of the model. In this study, we derive kinetic coefficients of activation and inactivation gates in ion channels by Onsager reciprocity theorem for an ensemble of gating particles, and propose that the obtained kinetic coefficients can be used as a comparative tool for the empirical validity of fitted rate constant functions to experimental data. We also illustrate its applicability based on the activation and inactivation kinetics of T-type calcium channel in thalamic relay neurons. We show that the shape of the steady-state curve by itself seems to be a poor indicator of the functional form of the rate functions, but the time constant curves reflect considerable variation depending on the particular form of the rate functions, and that the kinetic coefficients related to the time constants provide a powerful tool to determine the empirical validity of the fitted rate constants.

Humans↗

An improved non-linear thermodynamic model of voltage-dependent ionic currents.

Thermodynamic models of ionic currents are used to deduce exact functional form of rate constant. It is first assumed that free energy depends linearly on voltage. A major criticism of this approach is that time constant can reach arbitrarily small values resulting in an aberrant behavior. Recently, non-linear effects of electric field on the free energy were considered to solve this problem based on T-type calcium channel. In this study, we show that the current model approximately captures the voltage-dependence of the time constant only in a specific range of voltage and does not provide saturation of the time constant outside this range. Then, we propose an improved non-linear thermodynamic model and illustrate its applicability based on T-type calcium channel.

Animals↗

Activation kinetics of T-type calcium channel by a path probability approximation.

We previously formulated dynamics of ion channel gates by the path probability method. In this study, we apply that theoretical approach to derive the activation rate kinetics of T-type calcium channel in thalamic relay neurons. We derive explicit expressions of the forward and backward rate constants and show that the proposed rate constants accurately capture form of the empirical time constant, and that they also provide its saturation to a constant value at depolarized membrane potentials. We also compare our derivations with linear and nonlinear thermodynamic models of rate kinetics obtained from the same calcium channel, and show that it is possible to capture saturation of the time constant for the depolarized membrane potentials by the only proposed rate constants.

Calcium↗

A new approach to define dynamics of the ion channel gates.

Voltage-gated ion channels are of great importance in the generation and propagation of electrical signals in the excitable cell membranes. How these channels respond to changes in the potential across the membrane has been a challenging problem, and different approaches have been proposed to address the mechanism of voltage sensing and gating in these channels. In this study, we attempt a new approach by considering a simple two-state gate system and applying the path probability method to construct a nonequilibrium statistical mechanical model of the system. The model which is based on the principles of statistical physics provides a firm physical basis for ion channel gating.

Cell Membrane↗

A computer software for simulating single-compartmental model of neurons.

In this paper, a new computer software package, Yalzer, is introduced for simulating single-compartmental model of neurons. Passive or excitable membranes with voltage-gated ion channels can be modeled, and current clamp and voltage clamp experiments can be simulated. In the Yalzer, first-order differential equations used to define the dynamics of the gate variables and the membrane potential are solved by two separate integration methods with variable time steps: forward Euler and exponential Euler methods. Outputs of the simulation are shown on a spreadsheet template for allowing flexible data manipulation and can be graphically displayed. The user can define the model in detail, and examine the excitability of the model and the dynamics of voltage-gated ion channels. The software package addresses to ones who want to run simple simulations of neurons without need to any programming language skills or expensive software. It can also be used for educational purposes.

Computer Simulation↗

A new methodology to define the equilibrium value function in the kinetics of (in)activation gates.

A voltage-gated ion channel is fundamental in generation and propagation of electrical signals in the excitable membranes. Dynamics of (in)activation gates of the ion channel is modeled by first-order kinetics. The equilibrium value function is crucial in the kinetics of the (in)activation gates for fitting experimental data. We present a new methodology to define the equilibrium value function based on the lowest approximation of the cluster variation method and the static properties in the molecular field approximation. The methodology allows for exploration of the gating dynamics.

Cluster Analysis↗