Merkel Cells Transduce and Encode Tactile Stimuli to Drive Aβ-Afferent Impulses

Abstract

SUMMARY Sensory systems for detecting tactile stimuli have evolved from touch-sensing nerves in invertebrates to complicated tactile end-organs in mammals. Merkel discs are tactile end-organs consisting of Merkel cells and Aβ-afferent nerve endings, and are localized in fingertips, whisker hair follicles and other touch-sensitive spots. Merkel discs transduce touch into slowly adapting impulses to enable tactile discrimination, but their transduction and encoding mechanisms remain unknown. Using rat whisker hair follicles, we show that Merkel cells rather than Aβ-afferent nerve endings are primary sites of tactile transduction, and identify the Piezo2 ion channel as the Merkel cell mechanical transducer. Piezo2 transduces tactile stimuli into Ca2+-action potentials in Merkel cells, which drive Aβ-afferent nerve endings to fire slowly adapting impulses. We further demonstrate that Piezo2 and Ca2+-action potentials in Merkel cells are required for behavioral tactile responses. Our findings provide insights into how tactile end-organs function and have clinical implications for tactile dysfunctions.

Regulation of Piezo2 Mechanotransduction by Static Plasma Membrane Tension in Primary Afferent Neurons

“…Interestingly, a previous study also shows that CD alleviates mechanical hyperalgesia in an animal model of inflammatory pain (33). In addition, we show that mechanical hypersensitivity induced by hypotonic solution is abolished by Gd 3ϩ , a blocker of Piezo2 channels (6,8). These findings support the idea that sensitization of Piezo2 mechanotransduction at least partially contributes to the behavioral mechanical hypersensitivity induced by hypotonic solution in our in vivo experiments.…”

Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes

“…Conditional knock-out of Piezo2 in Merkel cells only modestly affected firing in the dynamic phase, but profoundly attenuated the response in the static phase, decreasing the number of spikes and increasing inter-spike interval (7,8). Piezo2 knockdown in hair follicles suppressed firing at both dynamic and static phase (64). The discrepancy between these results could be due to the different origin of Merkel cells 64).…”

“…Piezo2 knockdown in hair follicles suppressed firing at both dynamic and static phase (64). The discrepancy between these results could be due to the different origin of Merkel cells 64). However, it appears that Piezo2 contributes to the mechanosensitivity of both neural and somatic components of the cutaneous Merkel cell organs and that the deletion of Piezo2 in Merkel cells leads to the inability of the sensory neurons to transmit afferent response in the typical slowly adapting manner.…”

“…Direct mechanical stimulation of dissociated murine Merkel cells with a glass probe evoked a rapidly desensitizing RuR-sensitive MA current, absent after conditional knock-out of Piezo2 in skin (7,8). Similarly, recordings from Merkel cells in an ex vivo whisker hair follicle preparation revealed rapidly desensitizing MA current inhibited by Gd 3ϩ , RuR, anti-Piezo2 antibody, or Piezo2 shRNA knockdown (64).…”

Putative Mechanoproteins in Vertebrate Cutaneous Mechanoreceptors-Are they at the Basis of the Mechanotransduction?

“…In the peripheral nervous system it has been detected in dorsal root ganglia neurons [20,62], Merkel discs (consisting of Merkel cells and Aβ-afferent nerve endings) (Figure 1g-1i) and isolated Merkel cells [20,[63][64][65][66], low-threshold mechanoreceptors that innervate both hairy and glabrous skin including Meissner corpuscles and lanceolate nerve endings [62]. Consistently animals deficient in Piezo2 show an almost complete deficit in light-touch sensation and proprioception without affecting other somatosensory functions [62,66].…”