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

Guy S Bewick* (Corresponding Author), Robert W Banks

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)90-104
Number of pages15
JournalCurrent Opinion in Physiology
Early online date17 Dec 2020
Publication statusPublished - Apr 2021

Bibliographical note

The work from ourlaboratoriesin thisreview wassupported by the Medical Research Council UK [grant number G0601253]; a Scottish Universities Life Science Alliance/
Eli Lilly studentship [grant number RBZ0174]; Tenovus Scotland [grant numbers OL 532 & G13/08].
We would sincerely like to thank Prof Chih-Cheng Chen, Prof Dr Stephan Kro¨ger, Dr Rade Durbaba and Dr Susan Pyner for extremely valuable comments during preparation of this manuscript.


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