Modeling the kinetic mechanisms of voltage-gated ion channels

Abstract

From neurons to networks, the kinetic properties of voltage-gated ion channels determine specific patterns of activity. In this chapter, we discuss how experimental data can be obtained and analyzed to formulate kinetic mechanisms and estimate parameters, and how these kinetic models can be tested in live neurons using dynamic clamp. First, we introduce the Markov formalism, as applied to modeling ion channel mechanisms, and the quantitative properties of single-channel and macroscopic currents obtained in voltage-clamp experiments. Then, we discuss how to design optimal voltage-clamp protocols and how to handle experimental artifacts. Next, we review the theoretical and practical aspects of data fitting, explaining how to define and calculate the goodness of fit, how to formulate model parameters and constraints, and how to search for optimal parameters. Finally, we discuss the technical requirements for dynamic-clamp experiments and illustrate the power of this experimental-computational approach with an example.