Differential encoding of mammalian proprioception by voltage-gated sodium channels.
| Title: | Differential encoding of mammalian proprioception by voltage-gated sodium channels. |
|---|---|
| Authors: | Espino CM; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.; Nagaraja C; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.; Ortiz S; Department of Biological Sciences, San José State University, San Jose, CA, USA.; Dayton JR; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.; Murali AR; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.; Undergraduate Program in Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA.; Ma Y; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.; Undergraduate Program in Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA.; Mann EL; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.; Postbaccalaureate Research Education Program at UC Davis, University of California, Davis, Davis, CA, USA.; Garlapalli S; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.; Undergraduate Program in Psychology, University of California, Davis, Davis, CA, USA.; Wohlgemuth RP; Department of Physiology, Neurobiology, and Behavior, University of California, Davis, Davis, CA, USA.; Brashear SE; Department of Physiology, Neurobiology, and Behavior, University of California, Davis, Davis, CA, USA.; Smith LR; Department of Physiology, Neurobiology, and Behavior, University of California, Davis, Davis, CA, USA.; Wilkinson KA; Department of Biological Sciences, San José State University, San Jose, CA, USA.; Griffith TN; Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA. |
| Source: | Science advances [Sci Adv] 2025 Jan 10; Vol. 11 (2), pp. eads6660. Date of Electronic Publication: 2025 Jan 08. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
| MeSH Terms: | Proprioception*/physiology ; NAV1.6 Voltage-Gated Sodium Channel*/metabolism ; NAV1.6 Voltage-Gated Sodium Channel*/genetics ; Mice, Knockout*; NAV1.1 Voltage-Gated Sodium Channel/genetics ; NAV1.1 Voltage-Gated Sodium Channel/metabolism ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/physiology ; Voltage-Gated Sodium Channels/metabolism ; Voltage-Gated Sodium Channels/genetics ; Animals ; Mice |
| Abstract: | Animals requiring purposeful movement for survival are endowed with mechanoreceptors, called proprioceptors, that provide essential sensory feedback from muscles and joints to spinal cord circuits, which modulates motor output. Despite the essential nature of proprioceptive signaling in daily life, the mechanisms governing proprioceptor activity are poorly understood. Here, we identified nonredundant roles for two voltage-gated sodium channels (NaVs), NaV1.1 and NaV1.6, in mammalian proprioception. Deletion of NaV1.6 in somatosensory neurons (NaV1.6cKO mice) causes severe motor deficits accompanied by loss of proprioceptive transmission, which contrasts with our previous findings using similar mouse models to target NaV1.1 (NaV1.1cKO). In NaV1.6cKO animals, we observed impairments in proprioceptor end-organ structure and a marked reduction in skeletal muscle myofiber size that were absent in NaV1.1cKO mice. We attribute the differential contributions of NaV1.1 and NaV1.6 to distinct cellular localization patterns. Collectively, we provide evidence that NaVs uniquely shape neural signaling within a somatosensory modality. |
| Comments: | Update of: bioRxiv. 2024 Aug 28:2024.08.27.609982. doi: 10.1101/2024.08.27.609982.. (PMID: 39253497) |
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| Grant Information: | R16 GM153600 United States GM NIGMS NIH HHS; R25 GM116690 United States GM NIGMS NIH HHS; K01 NS124828 United States NS NINDS NIH HHS; T32 GM135741 United States GM NIGMS NIH HHS; F31 NS134241 United States NS NINDS NIH HHS; T32 GM144303 United States GM NIGMS NIH HHS; P30 EY012576 United States EY NEI NIH HHS; R01 NS135005 United States NS NINDS NIH HHS; R25 NS112130 United States NS NINDS NIH HHS; T32 GM099608 United States GM NIGMS NIH HHS; R01 AR079545 United States AR NIAMS NIH HHS; F31 AR082695 United States AR NIAMS NIH HHS |
| Substance Nomenclature: | 0 (NAV1.6 Voltage-Gated Sodium Channel); 0 (NAV1.1 Voltage-Gated Sodium Channel); 0 (Scn8a protein, mouse); 0 (Voltage-Gated Sodium Channels) |
| Entry Date(s): | Date Created: 20250108 Date Completed: 20250108 Latest Revision: 20260410 |
| Update Code: | 20260410 |
| PubMed Central ID: | PMC11708877 |
| DOI: | 10.1126/sciadv.ads6660 |
| PMID: | 39772670 |
| Database: | MEDLINE |
Journal Article