Cellular function given parametric variation: excitability in the Hodgkin-Huxley model

TL;DR

This paper analyzes how the Hodgkin-Huxley model maintains reliable neuronal excitability despite parameter variability by identifying key combined parameters and the stabilizing role of slow inactivation.

Contribution

It introduces a simplified framework using structural and kinetic parameters to understand excitability stability and highlights slow inactivation as a homeostatic mechanism.

Findings

Excitability depends on two combined parameters, S and K.

Parametric fluctuations are manageable within the S-K plane.

Slow inactivation stabilizes excitability amid parameter changes.

Abstract

How is reliable physiological function maintained in cells despite considerable variability in the values of key parameters of multiple interacting processes that govern that function? Here we use the classic Hodgkin-Huxley formulation of the squid giant axon action potential to propose a possible approach to this problem. Although the full Hodgkin-Huxley model is very sensitive to fluctuations that independently occur in its many parameters, the outcome is in fact determined by simple combinations of these parameters along two physiological dimensions: Structural and Kinetic (denoted $S$ and $K$). Structural parameters describe the properties of the cell, including its capacitance and the densities of its ion channels. Kinetic parameters are those that describe the opening and closing of the voltage-dependent conductances. The impacts of parametric fluctuations on the dynamics of the system, seemingly complex in the high dimensional representation of the Hodgkin-Huxley model, are tractable when examined within the $S-K$ plane. We demonstrate that slow inactivation, a ubiquitous activity-dependent feature of ionic channels, is a powerful local homeostatic control mechanism that stabilizes excitability amid changes in structural and kinetic parameters.