Scn10a, encoding the neuronal voltage-gated sodium channel NaV1.8, is associated with multiple physiological and pathological processes. It plays a role in cardiac electrophysiology, pain perception, and is also linked to various diseases. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions [1,2].

In mouse models, disruption of the intronic enhancer of Scn10a led to reduced cardiac Scn10a-short expression, decreased cardiac sodium current in atrial cardiomyocytes, atrial conduction slowing, and arrhythmia. The Scn10a-short transcript, expressed in cardiomyocytes of the atria, sinoatrial node, and ventricular conduction system, impacts NaV1.5-mediated sodium current and heart rhythm. Complete loss-of-function or knockout (KO) of Scn10a in rodent models decreased sensitivity to various pain stimuli [1,2].

In conclusion, Scn10a is crucial for cardiac conduction and pain perception. Mouse KO models have revealed its role in cardiac arrhythmias and pain-related pathophysiological mechanisms. Understanding Scn10a's functions provides insights into related diseases, such as atrial fibrillation, Brugada syndrome, and pain-related disorders [1,2,3].

References:

1. Man, Joyce C K, Bosada, Fernanda M, Scholman, Koen T, Barnett, Phil, Christoffels, Vincent M. 2021. Variant Intronic Enhancer Controls SCN10A-short Expression and Heart Conduction. In Circulation, 144, 229-242. doi:10.1161/CIRCULATIONAHA.121.054083. https://pubmed.ncbi.nlm.nih.gov/33910361/

2. Xue, Yaping, Chidiac, Celeste, Herault, Yann, Gaveriaux-Ruff, Claire. 2021. Pain behavior in SCN9A (Nav1.7) and SCN10A (Nav1.8) mutant rodent models. In Neuroscience letters, 753, 135844. doi:10.1016/j.neulet.2021.135844. https://pubmed.ncbi.nlm.nih.gov/33775738/

3. Huang, Yan, Chen, Xiao-Meng, Barajas-Martinez, Hector, Antzelevitch, Charles, Hu, Dan. . Common variants in SCN10A gene associated with Brugada syndrome. In Human molecular genetics, 31, 157-165. doi:10.1093/hmg/ddab217. https://pubmed.ncbi.nlm.nih.gov/34312669/