Differential Encoding of Mammalian Proprioception by Voltage-gated Sodium Channels

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2025 Jan 8

PMID 39772670

Authors

Cyrrus M Espino

Chetan Nagaraja

Serena Ortiz

Jacquelyn R Dayton

Akash R Murali

Yanki Ma

Emari L Mann

Snigdha Garlapalli

Ross P Wohlgemuth

Sarah E Brashear

Lucas R Smith

Katherine A Wilkinson

Theanne N Griffith

Affiliations

Soon will be listed here.

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 (Nas), Na1.1 and Na1.6, in mammalian proprioception. Deletion of Na1.6 in somatosensory neurons (Na1.6 mice) causes severe motor deficits accompanied by loss of proprioceptive transmission, which contrasts with our previous findings using similar mouse models to target Na1.1 (Na1.1). In Na1.6 animals, we observed impairments in proprioceptor end-organ structure and a marked reduction in skeletal muscle myofiber size that were absent in Na1.1 mice. We attribute the differential contributions of Na1.1 and Na1.6 to distinct cellular localization patterns. Collectively, we provide evidence that Nas uniquely shape neural signaling within a somatosensory modality.

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