Models of Electrical Activity: Calibration and Prediction Testing on the Same Cell

Mathematical models are increasingly important in biology, and testability is becoming a critical issue. One limitation is that one model simulation tests a parameter set representing one instance of the biological counterpart, whereas biological systems are heterogeneous in their properties and behavior, and a model often is fitted to represent an ideal average. This is also true for models of a cell's electrical activity; even within a narrowly defined population there can be considerable variation in electrophysiological phenotype. Here, we describe a computational experimental approach for parameterizing a model of the electrical activity of a cell in real time. We combine the inexpensive parallel computational power of a programmable graphics processing unit with the flexibility of the dynamic clamp method. The approach involves 1), recording a cell's electrical activity, 2), parameterizing a model to the recording, 3), generating predictions, and 4), testing the predictions on the same cell used for the calibration. We demonstrate the experimental feasibility of our approach using a cell line (GH4C1). These cells are electrically active, and they display tonic spiking or bursting. We use our approach to predict parameter changes that can convert one pattern to the other.