Cellular function given parametric variation: excitability in the Hodgkin-Huxley model
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.
Code (0)
등록된 구현이 없습니다.
Similar Papers 제목 키워드 기반
A memristive model of spatio-temporal excitability
This paper introduces a model of excitability that unifies the mechanism of an important neuronal property both in time and in space. As a starting point, we revisit both a key model of temporal excitability, proposed by…
modelFunctional effects of schizophrenia-linked genetic variants on intrinsic single-neuron excitability: A modeling study
Background: Recent genome-wide association studies (GWAS) have identified a large number of genetic risk factors for schizophrenia (SCZ) featuring ion channels and calcium transporters. For some of these risk factors, in…
Bioelectrical Interfaces Beyond Cellular Excitability: Cancer, Aging, and Gene Expression Reprogramming
Bioelectrical interfaces represent a significant evolution in the intersection of nanotechnology and biophysics, offering new strategies for probing and influencing cellular processes. These systems capitalize on the sub…
TranslationBiophysical models of intrinsic homeostasis: Firing rates and beyond
In view of ever-changing conditions both in the external world and in intrinsic brain states, maintaining the robustness of computations poses a challenge, adequate solutions to which we are only beginning to understand.…
Graphene oxide upregulates the homeostatic functions of primary astrocytes and modulates astrocyte-to-neuron communication
Graphene-based materials are the focus of intense research efforts to devise novel theranostic strategies for targeting the central nervous system. In this work, we have investigated the consequences of long-term exposur…