How do Calcium and Potassium conductance affect atrial fibrillation?
Fluctus (Group 3)
Maisam T. Begum
Joshua Finer
Peter Valdez
Atrial Fibrillation
• Over 2.2 million people in the US have atrial fibrillation (8 - 9% of people over 80).
• Blood clots can form, leading to a stroke.
• Some symptoms include irregular heart beats, chest pain, and shortness of breath.
• Still not well understood.
TNNP Model
• Based on experimental data.
• Attempts to more accurately represent the action potential than other models by including more than a minimal number of parameters.
• Computationally tractable (especially with progress in GPUs).
Conductance
• Calcium conductance: GCaL
• Potassium conductance: GKs
L Type Calcium Channels
• Generates inward Calcium current (ICaL).• Depolarizes cell.
Potassium Channels
• Generates outward Potassium current.• Hyperpolarizes cell.
• Includes slow outward Potassium current (IKs).
http://www.nature.com/nature/journal/v451/n7181/fig_tab/nature06799_F2.html
http://www.cvpharmacology.com/antiarrhy/cardiac_action_potentials.htm
Hypothesis
• Increasing GCaL would increase ICaL and make the spiral wave thicker.
• Increasing GKs would increase IKs and make the spiral wave thinner.
Methods• Parameter Range: 25% - 185%• Parameter Increment: 20%
GCal
GKs
Results
Loop & Hook
GCaL= 65% GKs= 145%
Drift
GCaL= 125% GKs= 85%
Spin
GCaL= 65% GKs= 65%
Discussion/Conclusion
• Our hypothesis was wrong since many of the spiral waves looked very similar.
• It is difficult to draw a conclusion since many of the spirals looked very similar.
• We think there might be a well-defined pattern of the spiral wave tip path.
Future Work
• Repeat simulations (with slight variations).
• Change more than 2 parameters at a time.
• Include the graphs of how membrane potential changes over time.
• Look at single individual periods.
Acknowledgments
• A special thanks to Dr. Griffeth, Dr. Fenton, Aron, Chuck, Rachel, Dan and CMACS.