Scn7a, also known as Nax, encodes an atypical voltage-gated sodium channel. Unlike typical family members, it has evolved to function as a concentration-dependent sensor of extracellular sodium ions, transducing signals related to extracellular sodium levels. It is involved in tissue homeostasis regulation, potentially detecting pathological extracellular sodium accumulation or endothelin signaling, and then triggering pro-inflammatory and pro-fibrotic responses [1].

In bone cancer pain rat models, enhanced expression of Scn7a/Nax in dorsal root ganglion neurons increased their excitability, contributing to pain. RNAi-mediated knockdown of Scn7a/Nax prevented the onset of hyperalgesia, indicating its role in bone cancer pain development [2].

In post-ganglionic sympathetic neurons, Scn7a/Nax allows them to directly sense elevated extracellular Na⁺, which could be related to sympathetic-driven hypertension as siRNA-mediated knockdown of Nax blocked the response to NaCl [3].

In temporal lobe epilepsy models, increased Scn7a/Na(x) expression was observed in neurons and reactive astrocytes during epileptogenesis and the chronic epileptic phase, suggesting its possible involvement in the epileptogenic process [4].

In conclusion, Scn7a plays essential roles in multiple biological processes and disease conditions. Its function as an extracellular sodium sensor is crucial in maintaining tissue homeostasis. Studies using gene-knockdown or knockout-like models in rats have revealed its significance in bone cancer pain, sympathetic-driven hypertension, and temporal lobe epilepsy, providing insights into potential therapeutic targets for these diseases.