Related Experiment Videos
Calculating the Consequences of Left-Shifted Nav Channel Activity in Sick Excitable Cells
Bela Joos1, Benjamin M Barlow2, Catherine E Morris3
1Department of Physics, University of Ottawa, Ottawa, ON, Canada. bjoos@uottawa.ca.
Handbook of Experimental Pharmacology
|October 15, 2017
Summary
Bleb damage to excitable cells causes "leaky" Nav channels, leading to Nav-Coupled Left Shift (Nav-CLS). This model predicts pathological excitability in damaged nerve tissue, aiding research and teaching.
Area of Science:
- Neuroscience
- Biophysics
- Computational Biology
Background:
- Sick excitable cells exhibit "leaky" sodium (Nav) channels and bleb damage to membranes.
- Bleb damage can induce kinetic changes in Nav channel function, termed Nav-Coupled Left Shift (Nav-CLS).
Purpose of the Study:
- To explain the development and application of the Nav-CLS model for predicting pathological excitability in damaged excitable cells.
- To provide a computational model for research and educational purposes.
Main Methods:
- Investigated kinetic changes in recombinant Nav1.6 channels in mechanically-blebbed cell-attached patches.
- Developed a computational model of Node of Ranvier excitability incorporating Nav-CLS and Na+/K+ ATPase activity.
- Coded the model in NEURON for simulation and analysis.
Main Results:
- Observed a damage-intensity-dependent, coupled hyperpolarizing shift in Nav1.6 activation and inactivation kinetics.
- Demonstrated that Nav-CLS, with Na+/K+ ATPase activity, sufficiently predicts pathological excitability phenomena.
- Generated a "Regimes" plot illustrating classes of excitability dysfunction.
Conclusions:
- The Nav-CLS model provides a robust framework for understanding and predicting excitability dysfunction in damaged nerve tissue.
- The NEURON-coded model is available for further research, large-scale tissue modeling, and educational use.