The Role of Cav1.1-Ca²⁺-IGF-1 in EMS Preventing Denervated Intrinsic Muscle Atrophy Induced by Brachial Plexus Injury

Functional recovery of the hand following brachial plexus injury (BPI) is highly dependent on preventing atrophy of the intrinsic muscles of the hand. Although electrical muscle stimulation (EMS) is an effective therapeutic approach for atrophy, its underlying mechanisms remain poorly elucidated. This study investigated the biological mechanisms through which EMS-induced muscle contraction inhibits the progression of denervation-induced atrophy. Using a rat model of total BPI, we validated the protective effect of EMS against atrophy in denervated intrinsic muscles. Whole-cell patch-clamp analysis confirmed the functional role of the L-type voltage-gated calcium channel in this process. We further discovered that EMS rectifies the aberrant elevation of intracellular Ca²⁺ concentration resulting from Cav1.1 dysfuntion. In vitro cellular experiments revealed that a rise in cytosolic Ca²⁺ activates the translation rather than transcription of IGF-1. Crucially, long-term and regular EMS sustains elevated IGF-1 levels, which subsequently modulates protein metabolism in myocytes, thereby mitigating denervated muscle atrophy.