Ion channels as biomarkers of altered myogenesis in myofiber precursors of Duchenne muscular dystrophy.

Autor: Cerchiara AG; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy., Imbrici P; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy., Quarta R; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy., Cristiano E; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy., Boccanegra B; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy., Caputo E; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy., Wells DJ; Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, UK., Cappellari O; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy., De Luca A; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, Bari, Italy.
Jazyk: angličtina
Zdroj: Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2024 Apr; Vol. 1534 (1), pp. 130-144. Date of Electronic Publication: 2024 Mar 22.
DOI: 10.1111/nyas.15124
Abstrakt: Myogenesis is essential for skeletal muscle formation, growth, and regeneration and can be altered in Duchenne muscular dystrophy (DMD), an X-linked disorder due to the absence of the cytoskeletal protein dystrophin. Ion channels play a pivotal role in muscle differentiation and interact with the dystrophin complex. To investigate ion channel involvement in myogenesis in dystrophic settings, we performed electrophysiological characterization of two immortalized mouse cell lines, wild-type (WT) H2K-2B4 and the dystrophic (DYS) H2K-SF1, and measured gene expression of differentiation markers and ion channels. Inward and outward currents/density increased as differentiation progressed in both WT and DYS cells. However, day-11 DYS cells showed higher (27%) inward current density with an increased expression ratio of Scn5a/Scn4a and decreased (48%) barium-sensitive outward current compared to WT. Furthermore, day-11 DYS cells showed more positive resting membrane potential (+10 mV) and lower membrane capacitance (50%) compared to WT. DYS cells also had reduced Myog and Myf5 expression at days 6 and 11. Overall, ion channel profile and myogenesis appeared altered in DYS cells. These results are a first step in validating ion channels as potential drug targets to ameliorate muscle degeneration in DMD settings and as differentiation biomarkers in innovative platforms.
(© 2024 The New York Academy of Sciences.)
Databáze: MEDLINE
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