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—Ca²⁺ transients measured in failing human ventricular myocytes exhibit reduced amplitude, slowed relaxation, and blunted frequency dependence. In the companion article (O’Rourke B, Kass DA, Tomaselli GF, Kääb S, Tunin R, Marbán E. Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart, I: experimental studies. Circ Res. 1999;84:562–570), O’Rourke et al show that Ca²⁺ transients recorded in myocytes isolated from canine hearts subjected to the tachycardia pacing protocol exhibit similar responses. Analyses of protein levels in these failing hearts reveal that both SR Ca²⁺ ATPase and phospholamban are decreased on average by 28% and that Na⁺/Ca²⁺ exchanger (NCX) protein is increased on average by 104%. In this article, we present a model of the canine midmyocardial ventricular action potential and Ca²⁺ transient. The model is used to estimate the …