Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy

Duchenne muscular dystrophy (DMD) is caused by the absence of the dystrophin protein and a properly functioning dystrophin-associated protein complex (DAPC) in muscle cells. DAPC components act as molecular scaffolds coordinating the assembly of various signaling molecules including ion channels. DMD shows a significant change in the functioning of the ion channels of the sarcolemma and intracellular organelles and, above all, the sarcoplasmic reticulum and mitochondria regulating ion homeostasis, which is necessary for the correct excitation and relaxation of muscles. This review is devoted to the analysis of current data on changes in the structure, functioning, and regulation of the activity of ion channels in striated muscles in DMD and their contribution to the disruption of muscle function and the development of pathology. We note the prospects of therapy based on targeting the channels of the sarcolemma and organelles for the correction and alleviation of pathology, and the problems that arise in the interpretation of data obtained on model dystrophin-deficient objects.

Automated summary

Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin protein and a properly functioning dystrophin-associated protein complex (DAPC) in muscle cells, which leads to significant changes in ion channel functioning and ion homeostasis regulation. This review analyzes current data on the structure, functioning, and regulation of ion channels in striated muscles in DMD, and discusses their contribution to muscle dysfunction and pathology. The review also explores the potential of therapy targeting sarcolemma and organelle channels for correcting and alleviating DMD pathology, as well as the challenges in interpreting data from dystrophin-deficient models.