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.