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J Physiol Volume 576, Number 1, 215-234, October 1, 2006 DOI: 10.1113/jphysiol.2006.113035
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NEUROSCIENCE

Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury

Olivier Poirot1, Temugin Berta2,3, Isabelle Decosterd2,3 and Stephan Kellenberger1

1 Department of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland
2 Anaesthesiology Pain Research Group, Department of Anaesthesiology, Lausanne University Hospital (CHUV), CH-1011 Lausanne, Switzerland
3 Department of Cell Biology and Morphology (DBCM), Faculty of Biology and Medicine, University of Lausanne, CH-1005 Lausanne, Switzerland

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.

(Received 5 May 2006; accepted after revision 11 July 2006; first published online 13 July 2006)
Corresponding author S. Kellenberger: Département de Pharmacologie et de Toxicologie, Université de Lausanne Rue du Bugnon 27, CH-1005 Lausanne, Switzerland. Email: stephan.kellenberger{at}unil.ch




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