Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury.
The H(+)-gated acid-sensing ion channels (ASICs) are expressed in dorsal root ganglion (DRG) neurones. Studies with ASIC knockout mice indicated either a pro-nociceptive or a modulatory role of ASICs in pain sensation. We have investigated in freshly isolated rat DRG neurones whether neurones with different ASIC current properties exist, which may explain distinct cellular roles, and we have investigated ASIC regulation in an experimental model of neuropathic pain. Small-diameter DRG neurones expressed three different ASIC current types which were all preferentially expressed in putative nociceptors. Type 1 currents were mediated by ASIC1a homomultimers and characterized by steep pH dependence of current activation in the pH range 6.8-6.0. Type 3 currents were activated in a similar pH range as type 1, while type 2 currents were activated at pH < 6. When activated by acidification to pH 6.8 or 6.5, the probability of inducing action potentials correlated with the ASIC current density. Nerve injury induced differential regulation of ASIC subunit expression and selective changes in ASIC function in DRG neurones, suggesting a complex reorganization of ASICs during the development of neuropathic pain. In summary, we describe a basis for distinct cellular functions of different ASIC types in small-diameter DRG neurones.
Poirot
Olivier
O
Département de Pharmacologie et de Toxicologie, Université de Lausanne Rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
Berta
Temugin
T
Decosterd
Isabelle
I
Kellenberger
Stephan
S
D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000293:injuries* / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009437:Neuralgia / Q000503:physiopathology; D009619:Nociceptors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D013111:Spider Venoms; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C490709:psalmopeotoxin I, Psalmopoeus cambridgei; D015032:Zinc; D002118:Calcium