Dynamics of neuromuscular junction degeneration after denervation: Mini review

Nerve pulses open the calcium channel on the sarcolemma, allowing calcium and sodium ions to enter the sarcoplasm. However, denervation changes the resting membrane potential to depolarize myofibers within hours with increased fibrillation activity. Increased influx of Ca2+ activates the dehydrogenases of Kreb's cycle, uncouples the oxidative phosphorylation, and increases the mitochondrial permeability through the opening of the permeability transition pore (PTP) and mitochondrial calcium uniporter (MCU) complex. Therefore, levels of free oxygen and nitrogen radicals are upregulated, to increase the inflammation and the main mechanisms including apoptosis, autophagy, and ubiquitin-proteasomal degradation of skeletal muscle atrophy. Increased Ca2+ pool also declines the mitochondrial ATP, activating AMP-activated protein kinase (AMPK) followed by forkhead box protein O3 (FoxO3) expression and increasing the incidence of mitophagy and ubiquitination of muscle proteins. Therefore, this current mini-review offers a comprehensive examination of denervation-induced muscle atrophy, shedding light on the intricate nature of regulatory mechanisms in cases of sciatic injury.