Cardiac arrhythmias in ion channel dysregulation

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Concept

Hi everyone, this is a project related to modeling cardiac tissue with the aim of attempting to understand the conditions under which pathological arrhythmias are evoked. These would include ventricular fibrillation and/or torsades de pointes. Specifically, it would be interesting to look at the the systemic effect of modulating myocyte function by altering specific ion channel parameters, though it would also be interesting to model the effects of myocardial infarction (dead/dying tissue in the heart due to heart attack).

Who's interested (add your name!)

• Vikas Shah
• Nathan Menke
• Kathryn Cooper
• Simon Angus
• John Mahoney

Questions to answer

• Can we create a minimal but useful model of cardiac tissue that appears to have normal function?
• What are the effects of perturbing ionic concentrations?
• What are the effects of perturbing ion channel functions?
• What are the effects of perturbing topological characteristics of the model (e.g. "damaging" part of the "heart")?

Background reading

• The laboratory of Yoram Rudy and colleagues (http://rudylab.wustl.edu/research/cell/index.html)
  • Provide C++ and Matlab sources code for very detailed single cell models of canine and guinea pig cardiac ventricular myocytes. These single cell models include descriptions of Na+, K+, Ca2+, and Cl- ion flows. They account for both Ca2+ release from intracellular stores and influx from extracellular environment. They also handle other more esoteric details.
  • http://rudylab.wustl.edu/research/cell/publications/propagation.htm Provides details of published work in which multicellular cardiac systems were modeled, using their single cell models, in order to model various electrophysiological phenomenal.
  • http://rudylab.wustl.edu/research/cell/publications/mutations.htm Gives an overview of the publications of the group looking at the effects of altering single channel parameters in order to examine the mechanism of arrhythmogenesis. Na+, K+, and Ca2+ channels have been examined.

Brainstorming ideas

• Want to avoid using an overt 3D model if possible. 2D with wraparound edges can provide a cylindrical sheet of cells which may provide a useful starting point, with more complicated topology or iterations if necessary. Using a circular 1D model may also be an appropriate strategy.

Sangus 07:54, 6 June 2007 (MDT) nice idea

• • so this would potentially give rise to a topological/local-interactions basis for synchronization (or not) in activity. Could a patch of cells which are under-supllied of some key signal transmitter in turn cause others to delay .. is there a native control system for this problem, if so, what if this is disrupted?
• "Modular" model as opposed to use of differential equation methods.
  • This would be akin to a cellular automata model if in 2D -- each grid place reacting to local environmental conditions and reacting accordingly