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Krause's corpuscles are typical of cutaneous mucous epithelia, like the lip vermillion or the glans clitoridis, and are associated with rapidly adapting low-threshold mechanoreceptors involved in gentle touch or vibration. PIEZO1 and PIEZO2 are transmembrane mechano-gated proteins that form a part of the cationic ion channels required for mechanosensitivity in mammalian cells. They are involved in somatosensitivity, especially in the different qualities of touch, but also in pain and proprioception. In the present study, immunohistochemistry and immunofluorescence were used to analyze the occurrence and cellular location of PIEZO1 and PIEZO2 in human clitoral Krause's corpuscles. Both PIEZO1 and PIEZO2 were detected in Krause's corpuscles in both the axon and the terminal glial cells. The presence of PIEZOs in the terminal glial cells of Kraus's corpuscles is reported here for the first time. Based on the distribution of PIEZO1 and PIEZO2, it may be assumed they could be involved in mechanical stimuli, sexual behavior, and sexual pleasure.

The clitoris is a leading player in female sexual arousal, if not the main protagonist. Despite this role, studies performed on this structure with specific neuroanatomical techniques are few. This study focuses on glans clitoris innervation, with special emphasis on sensory corpuscles and the presence of the mechanotransducer protein PIEZO2 in these structures. Six glans clitoris samples were obtained at autopsy covering an age spectrum between 52 and 83 years old. Several types of nerve terminations including free nerve endings, genital endbulbs as well as Meissner-like corpuscles and Pacinian corpuscles, but not Ruffini corpuscles, were found. Although corpuscular morphology in the glans clitoris was subtly different from the cutaneous digital counterparts, their basic composition was comparable for both Pacinian and Meissner-like corpuscles. Genital endbulbs showed heterogeneous morphology, and the axons usually exhibited a typical "wool ball" or "yarn ball" aspect. Some of them were lobulated and variably encapsulated by endoneurial elements (65%); from the capsule originate septa that divides the genital endbulbs, suggesting that they are found in clusters rather than as single corpuscles. In addition, most corpuscles in the glans clitoris showed axonal PIEZO2 immunoreactivity, thus, suggesting a mechanical role and molecular mechanisms of mechanosensibility similar to those of digital Meissner's corpuscles. Our results demonstrate that sensory corpuscles of the glans clitoris are similar to those of other glabrous skin zones, as most genital organs are characterized by clusters of corpuscles and the occurrence of the mechanoprotein PIEZO2 in the axons. These findings strongly suggest that PIEZO2 participates in erotic and sexual mechanical sensing., (© 2020 Anatomical Society.)

The transformation of mechanical energy into electrical signals is the first step in mechanotransduction in the peripheral sensory nervous system and relies on the presence of mechanically gated ion channels within specialized sensory organs called mechanoreceptors. Piezo2 is a vertebrate stretch-gated ion channel necessary for mechanosensitive channels in mammalian cells. Functionally, it is related to light touch, which has been detected in murine cutaneous Merkel cell-neurite complexes, Meissner-like corpuscles and lanceolate nerve endings. To the best of our knowledge, the occurrence of Piezo2 in human cutaneous mechanoreceptors has never been investigated. Here, we used simple and double immunohistochemistry to investigate the occurrence of Piezo2 in human digital glabrous skin. Piezo2 immunoreactivity was detected in approximately 80% of morphologically and immunohistochemically characterized (cytokeratin 20 + , chromogranin A + and synaptophisin + ) Merkel cells. Most of them were in close contact with Piezo2 - nerve fibre profiles. Moreover, the axon, but not the lamellar cells, of Meissner's corpuscles was also Piezo2 + , but other mechanoreceptors, i.e. Pacinian or Ruffini's corpuscles, were devoid of immunoreactivity. Piezo2 was also observed in non-nervous tissue, especially the basal keratinocytes, endothelial cells and sweat glands. The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner's corpuscles) low-threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch. These data offer additional insight into the molecular basis of mechanosensing in humans., (© 2017 Anatomical Society.)