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

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 its 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.

Automated summary

The debate over mechanosensory transduction in proprioceptors and low threshold mechanosensory nerve terminals has been ongoing for decades, with a focus on the role of ion channels in encoding stimulus speed and duration. Recent discoveries suggest that Piezo2 may play a key role in regulating the abundance of axolemmal MST complexes, potentially reconciling conflicting observations in the field.