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.
Sugiura
Takeshi
T
Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Bielefeldt
Klaus
K
Gebhart
G F
GF
D000138:Acidosis / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D048429:Cell Size; D002478:Cells, Cultured; D003106:Colon / Q000294:innervation*; D005071:Evoked Potentials; D045604:Extracellular Fluid / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008160:Lumbosacral Plexus / Q000166:cytology / Q000378:metabolism; D008297:Male; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013900:Thoracic Nerves / Q000166:cytology / Q000378:metabolism
D026941:Sodium Channel Blockers; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000584:Amiloride; C071423:capsazepine; D002211:Capsaicin