Calculating the consequences of left-shifted Nav channel activity in sick cells (Joos et al 2017)

 Download zip file 
Help downloading and running models
"Two features common to diverse sick excitable cells are “leaky” Nav channels and bleb damage-damaged membranes. The bleb damage, we have argued, causes a channel kinetics based “leakiness.” Recombinant (node of Ranvier type) Nav1.6 channels voltage-clamped in mechanically-blebbed cell-attached patches undergo a damage intensity dependent kinetic change. Specifically, they experience a coupled hyperpolarizing (left) shift of the activation and inactivation processes. The biophysical observations on Nav1.6 currents formed the basis of Nav-Coupled Left Shift (Nav-CLS) theory. Node of Ranvier excitability can be modeled with Nav-CLS imposed at varying LS intensities and with varying fractions of total nodal membrane affected. Mild damage from which sick excitable cells might recover is of most interest pathologically. Accordingly, Na+/K+ ATPase (pump) activity was included in the modeling. As we described more fully in our other recent reviews, Nav-CLS in nodes with pumps proves sufficient to predict many of the pathological excitability phenomena reported for sick excitable cells. ..."
1 . Joos B, Barlow BM, Morris CE (2017) Calculating the Consequences of Left-Shifted Nav Channel Activity in Sick Excitable Cells. Handb Exp Pharmacol [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): I K; I Na,t; I Sodium; Na/K pump;
Gap Junctions:
Gene(s): Nav1.6 SCN8A;
Simulation Environment: NEURON; Python;
Model Concept(s): Ion Channel Kinetics; Tutorial/Teaching;
Search NeuronDB for information about:  I Na,t; I K; I Sodium; Na/K pump;
Loading data, please wait...