DEVELOPMENT OF AUTOMATED SOFTWARE FOR ELECTROPHYSIOLOGY ANALYSES: EFFICIENT MODELLING OF ION CHANNELS IN EXCITABLE CELLS

Abstract

Cell and tissue simulations have largely contributed to a better understanding of the electrophysiological mechanisms underlying rhythmic movement in the heart and gastrointestinal tract, and to the discovery of new treatments for related pathologies. To model the activity of each type of ion channel expressed by a cell, experimentalists isolate their activity and collect data using patch-clamp experiments. Models are then developed and fitted manually against the data to try and mimick the channel’s behaviour in silico. However, such process is very tedious and requires many trial-and-error cycles to test different models. Here, we have developed a program which enables fast and efficient model development by automating the choice of model and the assessment of their goodness-of-fit. As a proof of concept, our algorithms were tested on existing data and returned models which either improve or perform as efficiently as models that were developed manually. We also tested our program on an experimental set of data and developed a new model for the Nav1.5 sodium channel. Therefore, we provide a solution to decrease the time and effort needed to model the activity of ion channels in the Hodgkin-Huxley framework.