Vasylyev Dmytro V, Liu Chuan-Ju, Waxman Stephen G
Department of Neurology and Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA.
Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, 06510, USA.
Trends Cell Biol. 2025 May;35(5):381-398. doi: 10.1016/j.tcb.2024.11.009. Epub 2024 Dec 31.
Voltage-gated sodium channels (VGSCs) are best known for their role in the generation and propagation of action potentials in neurons, muscle cells, and cardiac myocytes, which have traditionally been labeled as 'excitable'. However, emerging evidence challenges this traditional perspective. It is now clear that VGSCs are also expressed in a broad spectrum of cells outside the neuromuscular realm, where they regulate diverse cellular functions. In this review, we summarize current knowledge on the expression, regulation, and function of VGSCs in non-neuromuscular cells, highlighting their contributions to physiological processes and pathological conditions. Dynamic expression patterns of VGSCs in different cell types, involvement of VGSCs in cellular functions, such as phagocytosis, motility, and cytokine release, and their potential as therapeutic targets for diseases that include inflammatory disorders, osteoarthritis (OA), and cancer, are discussed. This new understanding of VGSCs and their effects on cells outside the neuromuscular realm opens new avenues for research and therapeutic interventions.
电压门控钠通道（VGSCs）最为人所知的是它们在神经元、肌肉细胞和心肌细胞动作电位的产生和传播中所起的作用，这些细胞传统上被标记为“可兴奋细胞”。然而，新出现的证据对这一传统观点提出了挑战。现在很清楚，电压门控钠通道也广泛表达于神经肌肉领域之外的各种细胞中，在这些细胞中它们调节多种细胞功能。在这篇综述中，我们总结了目前关于电压门控钠通道在非神经肌肉细胞中的表达、调节和功能的知识，强调了它们对生理过程和病理状况的贡献。讨论了电压门控钠通道在不同细胞类型中的动态表达模式、它们参与吞噬作用、细胞运动和细胞因子释放等细胞功能，以及它们作为包括炎症性疾病、骨关节炎（OA）和癌症等疾病治疗靶点的潜力。对电压门控钠通道及其对神经肌肉领域之外细胞影响的这种新认识为研究和治疗干预开辟了新途径。
