Mathematical modeling mechanisms of arrhythmias in transgenic mouse heart overexpressing TNF-

mias in transgenic mouse heart overexpressing TNF-. Am J Physiol Heart Circ Physiol 302: H934–H952, 2012. First published Novem-ber 11, 2011; doi:10.1152/ajpheart.00493.2011.—Transgenic mice overexpressing tumor necrosis factor- (TNF- mice) possess many of the features of human heart failure, such as dilated cardiomyopathy, impaired Ca2 handling, arrhythmias, and decreased survival. Al-though TNF- mice have been studied extensively with a number of experimental methods, the mechanisms of heart failure are not com-pletely understood. We created a mathematical model that reproduced experimentally observed changes in the action potential (AP) and Ca2 handling of isolated TNF- mice ventricular myocytes. To study the contribution of the differences in ion currents, AP, Ca2 handling, and intercellular coupling to the development of arrhyth-mias in TNF- mice, we further created several multicellular model tissues with combinations of wild-type (WT)/reduced gap junctio