Mathematical Properties of Pump-Leak Models of Cell Volume Control and Electrolyte Balance

TL;DR

This paper analyzes the mathematical properties of pump-leak models used for cell volume and electrolyte regulation, establishing conditions for the existence and stability of steady states using a free energy Lyapunov function.

Contribution

It provides the first rigorous analytical results on the existence and stability of steady states in pump-leak models, including cases with linear and nonlinear ion channel currents.

Findings

Unique globally stable steady state when ion currents are linear.

Cell volume tends to infinity if no steady state exists.

Stable steady state exists if pump current is not too large.

Abstract

Homeostatic control of cell volume and intracellular electrolyte content is a fundamental problem in physiology and is central to the functioning of epithelial systems. These physiological processes are modeled using pump-leak models, a system of differential algebraic equations that describes the balance of ions and water flowing across the cell membrane. Despite their widespread use, very little is known about their mathematical properties. Here, we establish analytical results on the existence and stability of steady states for a general class of pump-leak models. We treat two cases. When the ion channel currents have a linear current-voltage relationship, we show that there is at most one steady state, and that the steady state is globally asymptotically stable. If there are no steady states, the cell volume tends to infinity with time. When minimal assumptions are placed on the properties of ion channel currents, we show that there is an asymptotically stable steady state so long as the pump current is not too large. The key analytical tool is a free energy relation satisfied by a general class of pump-leak models, which can be used as a Lyapunov function to study stability.