In many mammalian cardiac tissues, molecular heterogeneity of repolarizing currents produces significant spatial heterogeneity and/or dispersion of repolarization. However, the ability of the mouse heart to sustain physiologically relevant heterogeneity of repolarization has recently been questioned, based on the small size of the murine heart. We used our previously published comprehensive computer model of the mouse action potential (Bondarenko et al. 2004) to predict the ability of mouse cardiac tissue to maintain spatial gradients of repolarization due to differential expression of membrane channels. Our model tissue consisted of two cell types (apex and septum) arranged as either a linear fiber (cable) or a ring. Adjacent myocytes were connected by gap junctions. The approximate circumference of the mouse heart surface is ~19 mm. Our tissue model was therefore constructed of 190 cells, which, given an average cell length of ~100 μm, approximates the dimensions of the mouse heart. Our simulations of action potential (AP) propagation in multicellular rings or cables predict that substantial gradients in repolarization and intracellular [Ca²⁺]_i transients can be maintained through heterogeneity of expression of K⁺ channels over a distance of about ten cells. This gradient can cause transient block of propagation. Simulation of AP propagation in inhomogeneous (with an abrupt inhomogeneity between apical and septal cells) and uniform (apex) cables stimulated from the apex with pacing period τ = 69 ms showed block at the boundary of the two cell phenotypes due to differential repolarization at high stimulation rates. This block was caused by a transient increase in AP duration in the septum region of the tissue model, which was the result of inactivation of slowly recovering K⁺ currents. In contrast, the AP in the uniform apical tissue showed only periodic behavior. In addition, the abruptness of gradients of ion channel expression as well as the site of stimulation were capable of causing [Ca²⁺]_i transient oscillations and affected the stability of [Ca²⁺]_i dynamics. Alternans occurred as a result of a complex interaction between the ionic and electrotonic currents and the Ca²⁺ fluxes in the cell, when exposed to repeated rapid stimulation. The major impact of this growing complexity is on the gating behavior of the ryanodine sensitive Ca²⁺ release mechanism in the sarcoplasmic reticulum. When abrupt channel expression gradients were introduced, alternans was observed at slower pacing rates than when gradual changes were used. Our simulations demonstrate that microscopic aspects of tissue organization are important for predicting large scale propagation phenomena and that the mouse heart should be able to sustain substantial molecularly based heterogeneity of repolarization.