A mechanically activated ion channel is functionally expressed in the MrgprB4 positive sensory neurons, which detect stroking of hairy skin in mice

Abstract

Mas-related G-protein coupled receptor B4 (MrgprB4) has been reported to be expressed in the dorsal root ganglion (DRG) neurons which detect stroking of hairy skin of mice. However, the mechanisms by which the MrgprB4 positive (+) neurons respond to adequate stimulus remain unsolved as it was also reported that electrophysiological analysis of cultured MrgprB4+ neurons did not reveal responses to mechanical stimuli. Contrary to the observation, however, in this study we show that the MrgprB4+ neurons functionally express a mechanically activated channel using DRG neurons dissociated from genetically-modified mice whose MrgprB4+ neurons express a red fluorescent protein. Hypotonicity-induced cell swelling increased intracellular Ca2+ concentrations ([Ca2+]i) of MrgprB4+ neurons. The [Ca2+]i increases were prevented by extracellular Ca2+ removal and by applications of nonselective Piezo channel blockers. Patch clamp analysis revealed that the MrgprB4+ neurons exhibited rapidly-adapting mechanically-activated currents. The MrgprB4+ neurons were stained with anti-Piezo2 antibody. These results raise the possibility that the MrgprB4+ neurons directly detect the stroking-like stimuli of hairy skin.