Effects of rapid and slow potassium repolarization currents and calcium dynamics on hysteresis in restitution of action potential duration.
We used a mathematical model to investigate effects of repolarizing currents I(kr) and I(ks), calcium (Ca) current I(CaL), and Ca dynamics in network sarcoplasmic reticulum and junctional sarcoplasmic reticulum (JSR) on hysteresis in restitution of action potential duration. Enhanced I(kr) increased slope of restitution, hysteresis loop thickness, and delay between peaks of diastolic intervals and action potential duration. Increase in I(ks) decreased loop thickness and peak delay. Decrease in I(CaL) had effects similar to increasing I(kr), except slope of restitution decreased markedly. Uptake of Ca into the network sarcoplasmic reticulum had less effect on hysteresis than transfer of Ca into JSR. Faster transfer of Ca into JSR markedly decreased loop thickness and peak delay. Our results provide insight into mechanisms responsible for this newly identified property of restitution. Such information will be valuable in studies where modification of hysteresis is used to investigate its role in arrhythmogenesis.
Wu
Runze
R
Center for Biomedical Engineering, University of Kentucky, KY 40506-0070, USA.
Patwardhan
Abhijit
A
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D006329:Heart Conduction System / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*
D015221:Potassium Channels; D011188:Potassium; D002118:Calcium