*8.1. Electrophysiologic Characteristics*

Arrhythmias are observed in a mouse model of DMD after acute β-adrenergic stimulation. In men, a case reported arrhythmic storm after abrupt withdrawal of beta-blocker therapy [103]. Arrhythmia may be linked to aberrant expression and remodeling of the cardiac gap junction protein connexin43 (Cx43). Opening of remodeled Cx43 hemichannels plays a key role in the development of arrhythmias in DMD mice. Then, these channels can be therapeutic targets to prevent fatal arrhythmias in patients with DMD [104].

DMD patients are prone to ventricular arrhythmias, which may be caused by abnormal calcium (Ca2<sup>+</sup>) homeostasis and elevated reactive oxygen species. In an animal model of DMD, a susceptibility to pacing induced ventricular arrhythmias was demonstrated. Oxidated Ca2+/calmodulin-dependent protein kinase II, Ox-CaMKII, promotes aberrant sarcoplasmatic reticulum Ca2<sup>+</sup> release through RyR2, which leads to delayed afterdepolarizations and triggered ventricular arrhythmias. Genetic inhibition of ox-CaMKII normalized intracellular Ca2<sup>+</sup> and prevented ventricular arrhythmias in this model [105].
