Background: Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is associated with severe cardiac complications including cardiomyopathy and cardiac arrhythmias. Recent research suggests that impaired voltage-gated ion channels in dystrophic cardiomyocytes accompany cardiac pathology. The existing knowledge, however, is very limited, and it is unknown if the ion channel defects are primary effects of dystrophic gene mutations, or secondary effects of the developing cardiac pathology. Methodology: Single ventricular cardiomyocytes from wild type and dystrophic neonatal mice prior to cardiomyopahty development, and cardiomyocytes from wild type and dystrophic adult mice with evident cardiomyopathy were isolated. The function of voltage-gated sodium-, calcium- and potassium-channels was investigated by using the whole cell patch clamp technique. Physiological consequences were followed up by investigating action potentials and by comparing surface ECG recordings in wt and dystrophic mice. Besides the most common model for DMD, the dystrophin-deficient mdx mouse, the present study is amongst the very first that also included mice additionally carrying a mutation in the utrophin gene. Principal Findings: In dystrophic neonatal cardiomyocytes voltage-gated sodium- current was found markedly reduced by 25 %. Additionally, extra utrophin-deficiency significantly altered sodium-channel gating parameters. The reduction of sodium-current got aggravated in the adult heart and with the additional knockout of utrophin. Calcium-channel inactivation was reduced in dystrophic neonatal and adult cardiomyocytes, and current density was increased only in dystrophic adult cardiomyocytes. Finally, inward rectifying potassium-current was diminished in dystrophic adult cardiomyocytes. The ion channel impairments observed, especially the reduction in sodium-current density, had direct effects on the action potential, as it slowed the upstroke and reduced the maximal depolarisation level. Action potential parameters were found even more distorted when ion channel impairments were interpolated to the human case as shown by computer simulations. Surface ECG recordings revealed a profound acceleration of the atrioventricular node conduction time, a delay in ventricular conduction and subtle differences in the ventricular repolarisation time. Conclusions/Significance: Significant impairments of voltage-gated sodium-, calcium- and potassium-currents exist in dystrophic cardiomyocytes. Concomitant changes in action potentials and ECGs indicate their functional and clinic relevance. Importantly, several of these ion channel impairments precede pathology development in the dystrophic heart, and may thus be considered potential cardiomyopathy triggers.