#Muscle spindle and golgi tendon organ skin

Here, we found that Pvalb + sensory neurons, which correspond primarily to proprioceptors 19, express nonselective MA cationic currents whose biophysical properties are consistent with Piezo2 channels 12, 16.

#Muscle spindle and golgi tendon organ skin

In mice, Piezo1 plays a critical role in vascular remodeling and red blood cell volume regulation 13, 15, 18, while Piezo2 is expressed in sensory neurons and functions as the mechanotransducer for low threshold mechanoreceptors in murine skin 14, 16, 17. Piezo family members are nonselective cation channels with diverse roles in mechanotransduction and volume signaling 12– 18.

However, no strong evidence has been provided for ENaC proteins in mammalian proprioception 4, 11. Consistent with this observation, ENaC proteins are expressed in rat MSs 11.

Previous studies have suggested that MA currents in mammalian proprioceptive neurons are largely mediated by Na + ions, with Ca 2+ ions playing a minor role 10. In mammals, however, the molecular mechanism underlying proprioception has remained largely elusive. More recently, DmPiezo has also been shown to mediate stretch-activated firing of larval Drosophila dorsal bipolar dendritic (dbd) neurons 9. elegans, trp-4 (a TRPN/NompC homolog) and unc-8 (a DEG/ENaC family member) are implicated in proprioception as mutations in these genes cause impaired movement in worms 7, 8. In Drosophila, the TRPN/NompC channel is expressed in both bipolar dendrite (bd) and class I dendritic arborization (da) proprioceptive neurons, and is required for proper larval crawling and behavioral coordination in adult flies 5, 6. In particular, the identification of ion channel(s) that are thought to transduce mechanical strain experienced by muscles and joints into electrical signals has been a major topic of research, and has been focused on Transient Receptor Potential (TRP) and Degenerin/Epithelial Na + Channel (DEG/ENaC) families 4. The molecular mechanism(s) underlying proprioception has been a long-standing question. MS afferents innervate intrafusal muscle fibers and detect changes in muscle length, whereas GTO afferents innervate the tendon organs at the myo-tendinous junction and respond to changes in muscle tone 2, 4. In mammals, proprioceptors represent anatomically distinct sensory neurons that have cell bodies in dorsal root ganglia (DRG) and innervate two distinct mechanoreceptors in skeletal muscles: muscle spindles (MSs) and Golgi tendon organs (GTOs) 2, 4. the ability to touch one’s nose with eyes closed) sensations and is required for basic motor functions such as standing and walking 3. The information encoded by proprioceptors contributes to both unconscious (e.g. Proprioception is the sense of body and limb position and is transduced by proprioceptive sensory neurons 1, 2.

Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors. Moreover, the mechanosensitivity of Pvalb + neurons that predominantly mark proprioceptors are dependent on Piezo2 in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings is dramatically reduced in Piezo2-deficient mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons show severely uncoordinated body movements and abnormal limb positions. Here we show that the mechanically activated (MA) nonselective cation channel Piezo2 is expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin, and joints.