An obvious difference between the regulatory action of the DAPC on Nav1.5 and Kir2.x channels in cardiomyocytes, which has emerged from our findings and previous studies, concerns the effect of the protein complex on channel expression. Thus, dystrophin-deficiency induces a substantial reduction in Nav1.5 channel expression,7,8 but has no (the present study) or only minor7 effect on Kir2.1 protein levels. This suggests that the decreased IK1 in dystrophin-deficient cardiomyocytes is not due to reduced Kir2.1 channel expression, but is caused by another mechanism. Because Kir2.1 channel localization in dystrophic cardiomyocytes may also be normal (Fig. 2C), channel inhibition by cytoplasmic regulatory factors is likely. Follow-up studies are needed to identify the responsible regulator(s). A better insight in how the DAPC regulates Kir2.x channels to control cardiac excitability, and how mutations in genes encoding for the involved proteins impair this regulation should increase our understanding of diseases associated with arrhythmias such as DMD, and may lead to improvements in therapy. Finally, DAPC regulation of inward rectifier potassium channels may also be relevant in other organs, e.g. the brain. Thus, in brains from mdx mice, dystrophin-deficiency was associated with a significant reduction in Kir4.1 mRNA expression and protein content.32