Mathematics Colloquia and Seminars
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Modeling Excitation-Contraction Coupling in a Rabbit Ventricular MyocyteMathematical Biology
|Speaker: ||Pepe Puglisi, UCD Pharmacology|
|Location: ||2112 MSB|
|Start time: ||Mon, Oct 19 2009, 3:10PM|
The processes initiated in the cell by membrane depolarization and ending in a contraction are termed: Excitation Contraction Coupling. Our lab incorporated a model of force generation/shortening development into a comprehensive mathematical description of the rabbit ventricular action potential (AP) and Ca2+ transient (LabHEART). This model allowed us to explore the effects of beta- adrenergic stimulation on myocyte contractility. The model was able to reproduce isotonic and isometric contractions and the classical curves of Force vs. Ca2+ and Force vs cell length relationships. Isoproterenol (ISO) application was simulated by altering L-type Ca2+ current, the slowly activating delayed rectifier K+ current, sarcoplasmic reticulum (SR) Ca2+ pump, SR Ca2+ leak, myofilaments Ca-sensitivity and cross-bridge cycling. The latter modification resulted essential to reproduce the ISO-induced increase in force generation/shortening development experimentally observed. AP duration (APD, for 90% of repolarization) adaptation to pacing frequencies was also examined. ISO shortened APD at all frequencies compared to control and flattened the adaptation curve, thus allowing an APD compatible with short cycle lengths (up to 5 Hz). This model provides a useful framework to study cardiac inotropy and constitutes a starting point to investigate electro-mechanical feedback in cardiac performance.