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The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice.
Neuroscience. 2006 May 12; 139(2):699-709.N

Abstract

A local elevation of H+-ion concentrations often occurs in inflammation and usually evokes pain by excitation of primary nociceptive neurons. Expression patterns and functional properties of the capsaicin receptor and acid-sensing ion channels suggest that they may be the main molecular substrates underlying this proton sensitivity. Here, we asked how the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) contribute to the proton response in subpopulations of nociceptive neurons from adult rats and mice (wildtype C57/Bl6, Balb/C and TRPV1-null). In cultured dorsal root ganglion neurons, whole cell patch clamp recordings showed that the majority of capsaicin-sensitive rat dorsal root ganglion neurons displayed large proton-evoked inward currents with transient ASIC-like properties. In contrast, the prevalence of ASIC-like currents was smaller in both mouse wildtype strains and more frequent in capsaicin-insensitive neurons. Transient ASIC-like currents were more frequent in both species among isolectin B4-negative neurons. A significantly reduced proton response was observed for dissociated dorsal root ganglion neurons in TRPV1 deficient mice. Unmyelinated, but not thin myelinated nociceptors recorded extracellularly from TRPV1-null mutants showed a profound reduction of proton sensitivity. Together these findings indicate that there are significant differences between rat and mouse in the contribution of TRPV1 and ASIC subunits to proton sensitivity of sensory neurons. In both species ASIC subunits are more prevalent in the isolectin B4-negative neurons, some of which may represent thin myelinated nociceptors. However, the main acid-sensor in isolectin B4-positive and isolectin B4-negative unmyelinated nociceptors in mice is TRPV1.

Authors+Show Affiliations

Department of Anesthesiology, University Erlangen-Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany. andreas.leffler@kfa.uni-erlangen.deNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16515841

Citation

Leffler, A, et al. "The Role of the Capsaicin Receptor TRPV1 and Acid-sensing Ion Channels (ASICS) in Proton Sensitivity of Subpopulations of Primary Nociceptive Neurons in Rats and Mice." Neuroscience, vol. 139, no. 2, 2006, pp. 699-709.
Leffler A, Mönter B, Koltzenburg M. The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice. Neuroscience. 2006;139(2):699-709.
Leffler, A., Mönter, B., & Koltzenburg, M. (2006). The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice. Neuroscience, 139(2), 699-709.
Leffler A, Mönter B, Koltzenburg M. The Role of the Capsaicin Receptor TRPV1 and Acid-sensing Ion Channels (ASICS) in Proton Sensitivity of Subpopulations of Primary Nociceptive Neurons in Rats and Mice. Neuroscience. 2006 May 12;139(2):699-709. PubMed PMID: 16515841.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice. AU - Leffler,A, AU - Mönter,B, AU - Koltzenburg,M, Y1 - 2006/03/03/ PY - 2005/06/13/received PY - 2005/12/13/revised PY - 2005/12/16/accepted PY - 2006/3/7/pubmed PY - 2006/8/1/medline PY - 2006/3/7/entrez SP - 699 EP - 709 JF - Neuroscience JO - Neuroscience VL - 139 IS - 2 N2 - A local elevation of H+-ion concentrations often occurs in inflammation and usually evokes pain by excitation of primary nociceptive neurons. Expression patterns and functional properties of the capsaicin receptor and acid-sensing ion channels suggest that they may be the main molecular substrates underlying this proton sensitivity. Here, we asked how the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) contribute to the proton response in subpopulations of nociceptive neurons from adult rats and mice (wildtype C57/Bl6, Balb/C and TRPV1-null). In cultured dorsal root ganglion neurons, whole cell patch clamp recordings showed that the majority of capsaicin-sensitive rat dorsal root ganglion neurons displayed large proton-evoked inward currents with transient ASIC-like properties. In contrast, the prevalence of ASIC-like currents was smaller in both mouse wildtype strains and more frequent in capsaicin-insensitive neurons. Transient ASIC-like currents were more frequent in both species among isolectin B4-negative neurons. A significantly reduced proton response was observed for dissociated dorsal root ganglion neurons in TRPV1 deficient mice. Unmyelinated, but not thin myelinated nociceptors recorded extracellularly from TRPV1-null mutants showed a profound reduction of proton sensitivity. Together these findings indicate that there are significant differences between rat and mouse in the contribution of TRPV1 and ASIC subunits to proton sensitivity of sensory neurons. In both species ASIC subunits are more prevalent in the isolectin B4-negative neurons, some of which may represent thin myelinated nociceptors. However, the main acid-sensor in isolectin B4-positive and isolectin B4-negative unmyelinated nociceptors in mice is TRPV1. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16515841/The_role_of_the_capsaicin_receptor_TRPV1_and_acid_sensing_ion_channels__ASICS__in_proton_sensitivity_of_subpopulations_of_primary_nociceptive_neurons_in_rats_and_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(05)01483-1 DB - PRIME DP - Unbound Medicine ER -