Figure 10. Proposed model of the role of NaV1.1 in proprioception.
Upon muscle static stretch, various channels activate, including Piezo2 (red), which results in an influx of calcium and sodium ions, causing a depolarization that activates NaV1.1 (dark blue). NaV1.1 activation drives reliable repetitive firing of proprioceptors during static stretch for normal motor behavior. Loss of NaV1.1 in sensory neurons results in inconsistent static firing at the afferent level while maintaining dynamic firing, resulting in uncoordinated movements and abnormal limb positioning. It is possible that a combination of Piezo2, NaV1.6 (yellow), NaV1.7 (pink), and/or other channels, such as glutamate receptors (dark blue), ASIC, and ENaC channels (green), mediates dynamic firing.