Sodium channels in non-excitable cells: powerful actions and therapeutic targets beyond Hodgkin and Huxley

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.