Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensoryneurons and proton-gated DEG/ENaC channels

Acidosis is associated with inflammation and ischemia and activates cation channels in sensory neurons. Inflammation also induces expression of FMRFam ide-like neuropeptides, which modulate pain. We found that neuropeptide FF (Phe-Leu-Phe-G In-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe ami de) generated no current on their own but potentiated H+-gated currents fro m cultured sensory neurons and heterologously expressed ASIC and DRASIC cha nnels. The neuropeptides slowed inactivation and induced sustained currents during acidification. The effects were specific; different channels showed distinct responses to the various peptides. These results suggest that aci d-sensing ion channels may integrate multiple extracellular signals to modi fy sensory perception.