Mechanotransduction channels in proprioceptive sensory nerve terminals: still an open question?

Bewick, Guy S; Banks, Robert W

Abstract

Mechanosensory transduction (MST) in proprioceptors, and other low threshold mechanosensory nerve terminals (LTMT), has been debated intensely for decades. MST in muscle spindles produces a receptor potential that encodes stimulus speed and duration, is predominantly due to Na+, a little Ca2+, plus some transient, non-mechanically-gated K+ ion fluxes. The abundant, multiple Na+-selective DEG/ENaC channel isoforms present in all LTMTs seemed obvious Na+ sources, perhaps supplemented with Ca2+-selective TRPs, and Ca2+-activated K+ channels. However, genetic deletions of even multiple DEG/ENaC genes produces only mild functional perturbation. Conversely, deleting the more recently discovered Piezo2 mechanosensory protein profoundly impairs LTMT responses, including in muscle spindles. Yet, its transient opening, non-Na+-selectivity and pharmacology do not reflect known receptor potential and response properties. A Ca2+-dependent recycling vesicle pool that we have shown is essential for mechanosensitivity, plus other recent DEG/ENaC discoveries, may reconcile these conflicting observations. We propose the abundance of axolemmal MST complexes, comprising untested DEG/ENaC combinations, is controlled by Piezo2-gated Ca2+ influx that regulates their vesicular insertion and retrieval.

Citation

Bewick, G. S., & Banks, R. W. (2021). Mechanotransduction channels in proprioceptive sensory nerve terminals: still an open question?. Current Opinion in Physiology, 20, 90-104. https://doi.org/10.1016/j.cophys.2020.11.007

• Journal Article Type: Article
• Online Publication Date: Dec 17, 2020
• Publication Date: 2021-04
• Deposit Date: Jan 20, 2021
• Publicly Available Date: Dec 17, 2021
• Journal: Current opinion in physiology.
• Print ISSN: 2468-8673
• Electronic ISSN: 2468-8673
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Pages: 90-104
• DOI: https://doi.org/10.1016/j.cophys.2020.11.007
• Keywords: Muscle spindle, low threshold mechanoreceptors, synaptic-like vesicle, Piezo, DEG/ENaC, transient receptor potential TRP
• Public URL: https://durham-repository.worktribe.com/output/1253559