SCN5A knock-down reduced contraction amplitude (-51.9% ± 37.2, p < 0.01) without inducing arrhythmias, whereas combined GJA5 and ATP1A1 knock-down induced significant irregularity (403% ± 371.3, p < 0.001), increased conduction heterogeneity (+18%), and reduced velocity (-52.4%). Here, ATP1A1 is linked to cardiac arrhythmia.