Geometry and nonlinear dynamics underlying excitability phenotypes in biophysical models of membrane potential

Abstract

The main goal of this dissertation was to study the bifurcation structure underlying families of low dimensional dynamical systems that model cellular excitability. One of the main contributions of this work is a mathematical characterization of profiles of electrophysiological activity in excitable cells of the same identified type, and across cell types, as a function of the relative levels of expression of ion channels coded by specific genes. In doing so, a generic formulation for transmembrane transport was derived from first principles in two different ways, expanding previous work by other researchers. The relationship between the expression of specific membrane proteins mediating transmembrane transport and the electrophysiological profile of excitable cells is well reproduced by electrodiffusion models of membrane potential involving as few as 2 state variables and as little as 2 transmembrane currents. Different forms of the generic electrodiffusion model presented here can be used to study the geometry underlying different forms of excitability in cardiocytes, neurons, and other excitable cells, and to simulate different patterns of response to constant, time-dependent, and (stochastic) time- and voltage-dependent stimuli. In all cases, an initial analysis performed on a deterministic, autonoumous version of the system of interest is presented to develop basic intuition that can be used to guide analyses of non-autonomous or stochastic versions of the model. Modifications of the biophysical models presented here can be used to study complex physiological systems involving single cells with specific membrane proteins, possibly linking different levels of biological organization and spatio-temporal scales.