期刊
CELLULAR SIGNALLING
卷 113, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2023.110970
关键词
VGSC; Na(V)1.4; Myoblasts; Skeletal muscle contraction; Action potentials; Muscle regeneration
类别
This study investigates the role of voltage-gated sodium channels (VGSC) in muscle regeneration. The findings suggest that with the progression of differentiation, VGSC expression and intracellular sodium concentration increase, and VGSC dynamics change, potentially contributing to muscle contraction.
Voltage-gated sodium channels (VGSC) are essential for triggering and relaying action potentials (AP), which perform critical functions in a variety of physiological processes, such as controlling muscle contractions and facilitating the release of neurotransmitters. In this study, we used a mouse C2C12 cell differentiation model to study the molecular expression and channel dynamics of VGSC and to investigate the exact role of VGSC in the development of muscle regeneration. Immunofluorescence, Real-time quantitative polymerase chain reaction, Western blot, and whole-cell patch clamp were employed for this purpose in mouse myoblasts. The findings revealed an increase in intracellular sodium concentration, Na(V)1.4 gene expression, and protein expression with the progress of differentiation (days 0, 1, 3, 5 and 7). Furthermore, VGSC dynamics exhibit the following characteristics: (1) The increase of sodium current (I-Na); (2) The decrease in the activation threshold and the voltage trigger maximum of I-Na; (3) A positive shift in the steady-state inactivation curve; (4) The recovery of I-Na during repolarization is delayed, the activity-dependent decay rate of I-Na was accelerated, and the proportionate amount of the fraction of activated channels was reduced. Based on these results, it is postulated that the activation threshold of AP could be decreased, and the refractory period could be extended with the extension of differentiation duration, which may contribute to muscle contraction. Taken together, VGSC provides a theoretical and empirical basis for exploring potential targets for neuromuscular diseases and other therapeutic muscle regeneration dysfunctions.
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