NaV1.1 and NaV1.6 Play Unique and Essential Roles in Muscle Spindle Afferent Function in Adult Mice

• DOI: 10.1152/physiol.2024.39.s1.1344
• Publication Date: 2024-05-21T14:57:50Z
• Authors: Serena Ortiz; Cyrrus Espino; Theanne N. Griffth; Katherine A. Wilk...
• Keywords: Muscle spindle

Voltage gated sodium channels (Na V s) are crucial for the generation and propagation of action potentials. There 9 different isoforms found in mammals 1.1-1.9), Na 1.1, 1.6, 1.7 muscle proprioceptors that sense stretch, spindle afferents. This sensory information is critical motor reflexes body limb position space. We previously mice lacking one or both copies 1.1 peripheral neurons displayed deficits, including intention tremors. Muscle afferents these also had unstable static stretch sensitivity but normal dynamic sensitivity, suggesting a specific deficit maintenance proprioceptor excitability when Piezo2 channel was likely to be closed (Espino, et al., 2022). hypothesized 1.6 would necessary behavior afferent function. generated neuron deletions by crossing fl/fl with expressing Pirt Cre cko ) observed severe deficits on open field rotarod test only (n=15) not Het (n=12) compared controls (n=8). In contrast we did observe used an ex vivo nerve preparation consisting extensor digitorum longus peroneal branch sciatic nerve. The maintained at length maximal twitch contraction (Lo) given battery ramp-and-hold stretches (2.5, 5, 7.5% Lo repeated 3 times each) 16 sinusoidal vibrations (5-100 μm amplitude; 10-100 Hz frequency). Preliminary results include recordings from 18 adult sexes n=8; n=10). were able find sensitive responses 10 mice, those severely impaired firing rates less than 5 Hz. contrast, robust slowly adapting all 8 mice. Only 1 any response vibration, suggests plays role initiating transmission, whereas essential maintaining during stretch. Future studies will determine whether loss 1.7, which does result alters work supported NIH Grant 5SC3GM127195 (KAW) RISE Fellowship 5R25GM71381 (SO), 5T32GM099608-10 1T32GM1144303-01A1 (CE). full abstract presented American Physiology Summit 2024 meeting available HTML format. no additional versions content this abstract. involved peer review process.