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

• Published in: Neuron (Cambridge, Mass.) Vol. 26; no. 1; pp. 133 - 141
• Main Authors: Askwith, C C, Cheng, C, Ikuma, M, Benson, C, Price, M P, Welsh, M J
• Format: Journal Article
• Language: English
• Published: United States 01-04-2000
• Subjects: Acid Sensing Ion Channels; Action Potentials - drug effects; Action Potentials - physiology; Animals; Cells, Cultured; Degenerin Sodium Channels; Epithelial Sodium Channels; FMRFamide; FMRFamide - pharmacology; FMRFamide - physiology; Ganglia, Spinal - drug effects; Ganglia, Spinal - physiology; Humans; Ion Channels - drug effects; Ion Channels - physiology; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - physiology; neuropeptide FF; Neuropeptides - pharmacology; Neuropeptides - physiology; Oligopeptides - pharmacology; Oligopeptides - physiology; Rats; Xenopus
• ISSN: 0896-6273
• DOI: 10.1016/S0896-6273(00)81144-7

Acidosis is associated with inflammation and ischemia and activates cation channels in sensory neurons. Inflammation also induces expression of FMRFamidelike neuropeptides, which modulate pain. We found that neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe amide) generated no current on their own but potentiated H+-gated currents from cultured sensory neurons and heterologously expressed ASIC and DRASIC channels. 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 acid-sensing ion channels may integrate multiple extracellular signals to modify sensory perception.