Voltage-gated sodium channel Nav1.1 is necessary for muscle spindle afferent function in adult mice

The sense of body and limb position, or proprioception, is necessary for producing coordinated and balanced movements. Muscle spindle (MS) afferents are responsible for transducing and transmitting muscle stretch information that is necessary for proprioception. The detection and transmission of muscle length information requires multiple isoforms of the voltage-gated sodium channel (NaV). Mutations to genes encoding Nav1.1 or Nav1.6 lead to motor movement disorders, and previous studies in our lab have shown that loss of Nav1.1 from birth results in a reduction in the ability of MS afferents to faithfully encode static stretch length. We hypothesized that Nav1.1 is still necessary for proper function after the MS has developed in adult mice. To test our hypothesis, we used a viral injection strategy to knock out the gene encoding Nav1.1, Scn1a. To target proprioceptors, we crossed mice expressing Cre in parvalbumin positive neurons (JAX #017320) with mice expressing Cre-dependent Cas9 under the Rosa 26 locus (JAX #026175). Two retroorbital injections one day apart of either a virus with sgRNAs targeting the Scn1a gene (AAV.PHP.s-sgNa V 1.1-FLEX-TdTomato; Nav1.1 cKO) or a control virus (AAV.PHP.s-sgLacZ-FLEX-TdTomatoa; Nav1.1 WT) were given to mice 21 to 25 days old. We waited until the mice were at least 2 months old and then extracted the extensor digitorum muscle with the sciatic nerve and placed it in a tissue bath. An extracellular glass electrode was used to record stretch-sensitive afferents and the muscle was stretched to three physiological lengths (2.5, 5, and 7.5% of optimal length). We were able to find stretch sensitive firing from MS afferents in 9 of 10 WT mice but only 4 of 8 cKO mice (χ 2 (1) = 3.23, p = 0.07). Similarly, all WT animals except 1 exhibited sustained firing over the entire 4 s stretch at all stretch lengths. In contrast, only 1 of 4 cKO mice had at least one afferent that could fire throughout the entire stretch (χ 2 (1) = 5.29, p = 0.02). This suggests that Nav1.1 is essential for MS afferent static stretch activity in adulthood. Future directions include increasing the sample size to have sufficient statistical power to compare whether the deficit is more severe with loss of Nav1.1 after development. If so, this would suggest that some compensation by the other Nav’s is possible if Nav1.1 is lost throughout development. This project was funded by the NIH NINDS R01NS135005 (TNG & KAW), NIGMS R16GM153600 (KAW) NINDS F31NS134241 (CE), the Alfred P. Sloan Foundation FG-2024-21522 (TNG), and an SJSU Student Research Fellowship (MM). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.