Functional effects of drugs and toxins interacting with Na_V1.4

Na(V)1.4 is a voltage-gated sodium channel subtype that is predominantly expressed in skeletal muscle cells. It is essential for producing action potentials and stimulating muscle contraction, and mutations in Na(V)1.4 can cause various muscle disorders. The discovery of the cryo-EM structure of Na(V)1.4 in complex with beta 1 has opened new possibilities for designing drugs and toxins that target Na(V)1.4. In this review, we summarize the current understanding of channelopathies, the binding sites and functions of chemicals including medicine and toxins that interact with Na(V)1.4. These substances could be considered novel candidate compounds or tools to develop more potent and selective drugs targeting Na(V)1.4. Therefore, studying Na(V)1.4 pharmacology is both theoretically and practically meaningful.