Mouse colon sensory neurons detect extracellular acidosis via TRPV1

Extracellular acidification contributes to pain by activating or modulating nociceptor activity. To evaluate acidic signaling from the colon, we characterized acid-elicited currents in thoracolumbar ( TL) and lumbosacral ( LS) dorsal root ganglion ( DRG) neurons identified by content of a fluorescent dye ( DiI) previously injected into the colon wall. In 13% of unidentified LS DRG neurons ( not labeled with DiI) and 69% of LS colon neurons labeled with DiI, protons activated a sustained current that was significantly and reversibly attenuated by the transient receptor potential vanilloid receptor 1 ( TRPV1) antagonist capsazepine. In contrast, 63% of unidentified LS DRG neurons and 4% of LS colon neurons exhibited transient amiloride- sensitive acid- sensing ion channel ( ASIC) currents. The peak current density of acid- elicited currents was significantly reduced in colon sensory neurons from TRPV1- null mice, supporting predominant expression of TRPV1 in LS colon sensory neurons, which was also confirmed immunohistochemically. Similar to LS colon DRG neurons, acid- elicited currents in TL colon DRG neurons were mediated predominantly by TRPV1. However, the pH producing half- activation of responses significantly differed between TL and LS colon DRG neurons. The properties of acid- elicited currents in colon DRG neurons suggest differential contributions of ASICs and TRPV1 to colon sensation and likely nociception.