Dynamic homeostasis in relaxation and bursting oscillations

Abstract

Homeostasis, broadly speaking, refers to the maintenance of a stable internal state when faced with external stimuli. Failure to manage these regulatory processes can lead to different diseases or death. Most physiologists and cell biologists around the world agree that homeostasis is a fundamental tenet of their disciplines. Nevertheless, a precise definition of homeostasis is hard to come by. Often times, homeostasis is simply defined as ``you know it when you see it''. Mathematical treatments of homeostasis involve studying equilibria of dynamical systems that are relatively invariant with respect to parameters. However, physiological processes are rarely static and often involve dynamic processes such as oscillations. In such dynamic environments, quantities such as average values may be relatively invariant with respect to parameters. This has been referred to as ``homeodynamics''. We present a general framework for homeodynamics involving systems with two or more time scales that elicits homeostasis in the temporal average of a species. The key point is that homeostasis manifests when measuring the slow variable responsible for driving oscillations and is not apparent in the fast variables. We demonstrate this in the Fitzhugh-Nagumo model for relaxation oscillations and then in two models for electrical bursting activity and calcium oscillations in pancreatic $β$-cells. One of these models has multiple slow variables, each driving the bursting oscillations in different parameter regimes, but homeodynamics is only present in the variable currently engaged in this role.