Journal article
ASIC3 and ASIC1 Mediate FMRFamide-Related Peptide Enhancement of H+-Gated Currents in Cultured Dorsal Root Ganglion Neurons
Journal of neurophysiology, Vol.89(5), pp.2459-2465
05/01/2003
DOI: 10.1152/jn.00707.2002
PMID: 12612000
Abstract
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.
Details
- Title: Subtitle
- ASIC3 and ASIC1 Mediate FMRFamide-Related Peptide Enhancement of H+-Gated Currents in Cultured Dorsal Root Ganglion Neurons
- Creators
- Jinghui Xie - Internal MedicineMargaret P Price - Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Departments ofJohn A Wemmie - Psychiatry, University of Iowa; and, Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242Candice C Askwith - Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Departments of, Internal MedicineMichael J Welsh - Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Departments of, Internal Medicine,, Physiology and Biophysics, and
- Resource Type
- Journal article
- Publication Details
- Journal of neurophysiology, Vol.89(5), pp.2459-2465
- DOI
- 10.1152/jn.00707.2002
- PMID
- 12612000
- NLM abbreviation
- J Neurophysiol
- ISSN
- 0022-3077
- eISSN
- 1522-1598
- Language
- English
- Date published
- 05/01/2003
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984003998402771
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