The well-known fact that disruption of the DAPC (due to dystrophin-deficiency) in cardiomyocytes significantly impairs Nav1.5 channel expression7,8 and function7-9 suggests that an intact DAPC is required to maintain normal Nav1.5 channel properties. In contrast, the notion that the DAPC is also important in the regulation of Kir2.x channel expression and function12 has remained purely speculative till this day. In the present study, we provide the first functional evidence that the DAPC indeed also impacts Kir2.x channels by showing that IK1 in dystrophin-deficient cardiomyocytes is substantially diminished. This suggests that, like Nav1.5 channels, Kir2.x channels require interaction with the DAPC for their proper functioning. In both cases, a disruption of dystrophin leads to a marked reduction in the respective current (INa and IK1, respectively). A reduced IK1 due to dystrophin-deficiency may provide an explanation for the low resting potentials measured in dystrophic cardiac8,28 and skeletal29-31 myocytes when compared to their healthy counterparts. It also represents a so far unknown potential mechanism to cause cardiac arrhythmias in DMD patients.