Kinetic Modeling of Voltage-Gated Channels

Creative Bioarray is dedicated to helping clients model the dynamics of voltage-gated ion channels in real time and analyze their biophysical properties. We are focused on deriving biophysically realistic models from macroscopic currents obtained from whole-cell voltage-clamp experiments and testing these models in living neurons using the dynamic clamp.

Introduction

In neurons and other excitable cells, voltage-gated ion channels play a uniquely important role and participate in a variety of physiological processes. They use specialized voltage-sensing structures to detect changes in membrane potential and turn on and off in response to these changes, which are important for action potential generation and propagation. To perform this function, channel molecules undergo conformational transitions within a set of conducting and non-conducting states, governed by specific kinetic mechanisms.

Different types of neurons display unique patterns of cellular excitability and assemble into brain circuits with different network properties. To understand the neuronal function, it is necessary to obtain an accurate model of the gating mechanism of ion channels and to explore the molecular properties of voltage-gated ion channels, especially the kinetics of state transitions and their voltage sensitivity. In recent years, advances in techniques such as whole-cell voltage-clamp experiments and dynamic clamp have provided the possibility to study the kinetic mechanisms of voltage-gated ion channels.

Fig. 1 Testing ion channel models in live neurons with dynamic clamp. (Salari, 2016)

Our Services

In order to help our clients simulate the dynamic mechanism of voltage-gated ion channels, we have established a new technology, dynamic clamping technology, as a quantitative tool for channel dynamics modeling. This technology is applicable to functional environments, neurons, or other excitable cells, and can accurately integrate realistic kinetic models. Combined with the progress we have made in software implementation, we can help clients find a model and parameter values to clarify the biophysical properties and complex dynamic mechanisms of voltage-gated ion channels. This technology involves the following steps:

• Establishment of computational models.
• Pharmacological block the current of the studied channel.
• Functionally replace the current of the channel with dynamic clamping, and adjust the parameters to spike recovery.
• Calculate the error between the action potential generated by the dynamic clamp and the "reference" action potential normally generated by the initial cell, and select the one with small error as the model and reference values.

We provide our clients with the following services:

• Functional testing of different kinetic models and accurate parameter estimation in real time by fitting action potential waveforms.
• Add the additional information to the action potential according to the specific model and parameter values to improve parameter identifiability and model discrimination.
• Tests for real-time fitting in computer simulations.
• Tests for real-time fitting in neurons.

With a team of experts with extensive experience in electrophysiological technology and computer modeling, Creative Bioarray has the strength to provide kinetic analysis services for voltage-gated ion channels, providing important information for your research to further study ion channels and membrane biophysics. If you are interested in our services, please contact us for more details.

Reference

1. Salari, A.; et al. Modeling the kinetic mechanisms of voltage-gated ion channels. Advanced patch-clamp analysis for neuroscientists. Humana Press, 2016: 267-304.