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