Mathematical modeling of cardiac excitation and arrhythmias
The Hund lab has expertise in the development of detailed mathematical models of cardiac cells and tissue to study the role of cell signaling networks in congenital and acquired forms of cardiac arrhythmia. We have developed physiological models of the cardiac action potential that incorporate critical cell signaling and targeting pathways. Computer simulations have identified an important role for abnormal cell signaling in ion channel changes and cardiac arrhythmia following myocardial infarction, as well as in several congenital arrhythmia syndromes (e.g. Timothy syndrome, ankyrin-B syndrome). The overall goal of this research is to identify ionic mechanisms responsible for ion channel dysfunction and cardiac arrhythmia.
Onal B, Gratz D and Hund TJ. Ca2+/calmodulin-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling and excitability: a mathematical modeling study. Am J Physiol Heart Circ Physiol. 2017;313:H1227-H1239.
Glynn P, Onal B, Hund TJ. Cycle length restitution in sinoatrial node cells: A theory for understanding spontaneous action potential dynamics. PLoS ONE. 2014; 9:e89049. PMCID:PMC3923067.
Wolf RM, Glynn P, Hashemi S, Zarei K, Mitchell CC, Anderson ME, Mohler PJ, and Hund TJ. Atrial fibrillation and sinus node dysfunction in human ankyrin-B syndrome: A computational analysis. Am J Physiol Heart Circ Physiol. 2013; 304:H1253-66. PMCID: PMC3652094.
Wolf RM, Mitchell CC, Christensen MD, Mohler PJ, and Hund TJ. Defining new insight into atypical arrhythmia: a computational model of ankyrin-B-syndrome. Am J Physiol Heart Circ Physiol. 2010; 299:H1505-H1514.
Christensen MD, Dun W, Boyden PA, Anderson ME, Mohler PJ, and Hund TJ. Oxidized calmodulin kinase II regulates conduction following myocardial infarction: A computational analysis. PLoS Comput Biol. 2009; 5:e1000583. PMCID: PMC2778128.
Hund TJ, Decker KF, Kanter E, Mohler PJ, Boyden PA, Schuessler RB, Yamada KA, Y Rudy. Role of activated CaMKII in abnormal calcium homeostasis and INa remodeling after myocardial infarction: Insights from mathematical modeling. J Mol Cell Cardiol. 2008;45:420-8. PMCID: PMC2587155.
Hund TJ and Y Rudy. Rate dependence and regulation of the action potential and calcium transient in a canine cardiac ventricular cell model. Circulation. 2004; 110:3168-3174