ASIC3 and ASIC1 Mediate FMRFamide-Related Peptide Enhancement of H+-Gated Currents in Cultured Dorsal Root Ganglion Neurons

• Published in: Journal of neurophysiology 2003-05, Vol.89 (5), p.2459-2465
• Main Authors: Xie, Jinghui, Price, Margaret P, Wemmie, John A, Askwith, Candice C, Welsh, Michael J
• Format: Article
• Language: English
• Subjects: Acid Sensing Ion Channels; Animals; Cells, Cultured; FMRFamide - pharmacology; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - physiology; Half-Life; Hydrogen-Ion Concentration; Ion Channel Gating - drug effects; Membrane Proteins; Mice; Nerve Tissue Proteins; Sodium Channels - drug effects; Sodium Channels - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00707.2002

  1 Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Departments of   2 Internal Medicine,   3 Physiology and Biophysics, and   4 Psychiatry, University of Iowa; and   5 Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242 Xie, Jinghui, Margaret P. Price, John A. Wemmie, Candice C. Askwith, and Michael J. Welsh. ASIC3 and ASIC1 Mediate FMRFamide-Related Peptide Enhancement of H + -Gated Currents in Cultured Dorsal Root Ganglion Neurons. J. Neurophysiol. 89: 2459-2465, 2003. The acid-sensing ion channels (ASICs) form cation channels that are transiently activated by extracellular protons. They are expressed in dorsal root ganglia (DRG) neurons and in the periphery where they play a function in nociception and mechanosensation. Previous studies showed that FMRFamide and related peptides potentiate H + -gated currents. To better understand this potentiation, we examined the effect of FMRFamide-related peptides on DRG neurons from wild-type mice and animals missing individual ASIC subunits. We found that FMRFamide and FRRFamide potentiated H + -gated currents of wild-type DRG in a dose-dependent manner. They increased current amplitude and slowed desensitization following a proton stimulus. Deletion of ASIC3 attenuated the response to FMRFamide-related peptides, whereas the loss of ASIC1 increased the response. The loss of ASIC2 had no effect on FMRFamide-dependent enhancement of H + -gated currents. These data suggest that FMRFamide-related peptides modulate DRG H + -gated currents through an effect on both ASIC1 and ASIC3 and that ASIC3 plays the major role. The recent discovery of RFamide-related peptides (RFRP) in mammals suggested that they might also modulate H + -gated current. We found that RFRP-1 slowed desensitization of H + -gated DRG currents, whereas RFRP-2 increased the peak amplitude. COS-7 cells heterologously expressing ASIC1 or ASIC3 showed similar effects. These results suggest that FMRFamide-related peptides, including the newly identified RFRPs, modulate H + -gated DRG currents through ASIC1 and ASIC3. The presence of several ASIC subunits, the diversity of FMRFamide-related peptides, and the distinct effects on H + -gated currents suggest the possibility of substantial complexity in modulation of current in DRG sensory neurons.