Piezo2 regulates colonic mechanical sensitivity in a sex specific manner in mice

Abstract

The mechanosensitive ion channel Piezo2 in mucosa and primary afferents transduces colonic mechanical sensation. Here we show that chemogenetic activation or nociceptor-targeted deletion of Piezo2 is sufficient to regulate colonic mechanical sensitivity in a sex dependent manner. Clozapine N-oxide-induced activation of Piezo2;hM3Dq-expressing sensory neurons evokes colonic hypersensitivity in male mice, and causes dyspnea in female mice likely due to effects on lung sensory neurons. Activation of Piezo2-expressing colonic afferent neurons also induces colonic hypersensitivity in male but not female mice. Piezo2 levels in nociceptive neurons are higher in female than in male mice. We also show that Piezo2 conditional deletion from nociceptive neurons increases body weight growth, slows colonic transits, and reduces colonic mechanosensing in female but not male mice. Piezo2 deletion blocks colonic hypersensitivity in male but not female mice. These results suggest that Piezo2 in nociceptive neurons mediates innocuous colonic mechanosensing in female mice and painful sensation in male mice, suggesting a sexual dimorphism of Piezo2 function in the colonic sensory system.

Piezo1 and Piezo2 channels in retinal ganglion cells and the impact of Piezo1 stimulation on light-dependent neural activity

“…S3E,F). These observations suggest the antibodies used in this study show reasonable specificity, in agreement with previous confirmation reported [50][51][52][53][54][55][56][57] , while also confirming the detection of message for both Piezo1 and Piezo2 in the RPE/choroid tissue above.…”

“…Additional support from others validates the staining of the antibodies used in this study, including KO mice models, reporter mice, pre-absorption assay, or genetically modified cell lines [50][51][52][53][54][55][56][57] .…”

Infiltrated macrophages aggravate TMJOA chronic pain via Piezo2 in IB4 + - TG neurons

“…Piezo2, a vital mechanosensitive ion channel for proprioception, touch, and bladder stretch sensation, is widely expressed in sensory neurons, indicating its critical physiological role during mechanical sensitization [43,44]. Based on our knowledge, it's the rst report regarding the upregulation of Piezo2 in TG neurons in TMJOA chronic pain rats.…”

Piezo1 in Digestive System Function and Dysfunction

“…Thus, the role of Piezo1 in direct ENS mechanotransduction should be interpreted cautiously. By comparison, many studies highlight the robust mechanosensitive role of Piezo2 in ENS [ 137 , 138 , 139 ]. We speculate the difference in mechanotransduction between Piezo1 and Piezo2 originates from the kinetics differences despite their similar structure.…”