Thursday, April 5, 2018 1pm to 2pm
About this Event
25 Park Place, Atlanta, GA
Speaker
Dr. Vladimir E Bondarenko, Mathematics & Statistics, Georgia State University
Title
“Modeling mouse cardiac electrophysiology: electrical activity, calcium dynamics, and β-adrenergic signaling”
Abstract
The β1- and β2-adrenergic signaling systems play different roles in the functioning of cardiac cells. Experimental data shows that the activation of β1-adrenergic signaling system produces significant inotropic, lusitropic, and chronotropic effects in the heart, such as increased magnitude and relaxation rates of calcium transients and contraction force, and increased heart rhythm, while the effects of the β2-adrenergic signaling system is less apparent. Excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure, while moderate overexpression of β2-adrenergic receptors improves cardiac function. To simulate these experimental findings three mathematical models of mouse ventricular myocytes were developed. The first model describes only β1-adrenergic signaling system, second model includes both β1- and β2-adrenergic signaling, and the third model describes mouse ventricular myocyte overexpressing β2-adrenergic receptors. The models describe the dynamics of major signaling molecules in different subcellular compartments; kinetics and magnitudes of phosphorylation of ion channels, transporters, and calcium handling proteins; modifications of action potential shape and duration; and calcium and sodium dynamics upon simultaneous stimulation of β1- and β2-adrenergic receptors, or during their separate stimulation. The third model reveals mechanisms of the differential effects of stimulation of β2-adrenoceptors in wild type and transgenic mice overexpressing β2-adrenoceptors.
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