Activity of self-depolarizing pacemaker cells bio-engineered in virtual heterogeneous ventricular tissue

Genetically engineered cardiac pacemakers are a proposed alternative or support to the state-of-the-art electronic devices. Down-regulation of the expression of Kir2.1 channels reduces the activity of the inward rectifier current I_K1 and turns ventricular cardiomyocytes to pacemaker cells. This effect was mimicked in computational cells describing heterogeneous human ventricular electrophysiology by blocking the I_K1 current. These intrinsic self-depolarizing cells were inserted into a long and thin parallelepipedal anatomical structure describing a ventricular strand from endocardium to epicardium. The width and position of the pacemaking region was variable. The required width for successfully driving the tissue mainly depended on the amount of adjacent normal ventricular myocytes. Attachment of the pacemaker region to any tissue boundary reduced the necessary size. The smallest width was required for attachment to the endocardium. The cycle length of spontaneous activation was smallest for endocardial attachment and decreased with the size of the self-depolarizing region.