The mechanosensitive ion channel Piezo2 is selectively expressed in enterochromaffin (EC) cells of the human and mouse gastrointestinal mucosa

BACKGROUND Enterochromaffin (EC) cells are enteroendocrine cells in the gastrointestinal (GI) epithelium that release serotonin (5‐HT) in response to a variety of stimuli including mechanical force. In turn, EC cell 5‐HT affects GI secretion, motility and sensation. The molecular mechanism of EC cell mechanotransduction is unknown. The recently discovered mechanosensitive ion channel Piezo2 is important in several mechanosensory cell types. AIM to determine if the mechanosensitive ion channel Piezo2 is expressed and functional in EC cells. METHODS Murine small bowel was collected, fixed in 4% paraformaldehyde, and frozen. Human and mouse RNA from human jejunum and mouse duodenum, jejunum and ileum was analyzed by quantitative RT‐PCR for Piezo2 mRNA. Piezo2 and 5‐HT were also identified by fluorescence immunolabeling. QGP‐1, a human enteroendocrine cell model, was analyzed by RT‐PCR for the presence of Piezo2 and immunolabeling was done to detect Piezo2 and 5‐HT. Piezo2 mechanically activated currents were recorded from QGP‐1 cells in whole‐cell configuration. Voltage‐clamped QGP‐1 cells were subjected to a series of mechanical perturbations using a piezo‐electrically driven glass probe at steps of 0.3 μm for stimulation. RESULTS Human jejunum and all segments of mouse small bowel mucosa (duodenum, jejunum, ileum) expressed Piezo2 mRNA. In human jejunum and all segments of mouse small bowel Piezo2 co‐localized with 5‐HT in >90% of 5‐HT containing cells. No Piezo2 immunoreactivity was seen outside of 5‐HT positive enterochromaffin cells. The enteroendocrine cell model QGP‐1 expressed both Piezo2 and 5‐HT by immunohistochemistry and RT‐PCR showed message for Piezo2. Application of force to the surface of voltage‐clamped QGP‐1 cells elicited whole cell fast inward non‐selective cation currents of ~200 pA (at −60 mV) that were blocked by Gd 3+ with kinetic properties compatible with Piezo2 channels. CONCLUSIONS Piezo2 is specifically expressed in human and murine small bowel EC cells and in the enteroendocrine cell model QGP‐1. QGP‐1 cells have a mechanosensitive inward cation current with kinetic and pharmacological properties similar to Piezo2. Our data suggest that Piezo2 is involved in EC cell mechanotransduction. Support or Funding Information Supported by NIH DK106456 , DK84567, DK052766