Duchenne muscular dystrophy (DMD) is an inherited disease characterized by progressive muscle weakness and degeneration. Besides the relatively well characterised skeletal muscle degenerative processes, DMD is also associated with severe cardiovascular complications including the development of cardiomyopathy and cardiac arrhythmias. The current understanding of the cardiac pathomechanisms is still very limited, but recent research suggests that dysfunctional ion channels in dystrophic cardiomyocytes may contribute. Here we used two mouse models for DMD, the dystrophin-deficient mdx mouse and the dystrophin/utrophin-deficient mdx-utr double knock-out mouse. By using the whole cell patch clamp technique, currents through voltage-gated L-type calcium channels were recorded in ventricular cardiomyocytes isolated from the hearts of adult wild type and dystrophic mice. We found significantly increased currents through calcium channels in dystrophic mdx and mdx-utr cardiomyocytes, when compared with wild type cardiomyocytes. In addition, calcium channel inactivation in dystrophic mdx and mdx-utr cells was slowed. Both effects enhance the calcium influx during an action potential, and generated altered surface electrocardiogram parameters in mdx and mdx-utr mice. Quantitative RT-PCR and preliminary Western Blot experiments suggest that the expression of calcium channel subunits (α1C, α2δ-1 and β2) was similar in wild type and dystrophic cardiac ventricles. Thus, the observed calcium channel abnormalities in dystrophic cardiomyocytes seem to result from alterations in channel regulatory processes. Hereto, data on channel regulation by PKA and nitric oxide synthases are shown.We conclude that enhanced calcium influx into dystrophic cardiomyocytes through L-type calcium channels may contribute to the cardiac pathology (e.g. arrhythmias) observed in DMD patients. Supported by the Austrian Science Fund FWF (P23060).