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Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons
Low voltage–activated (LVA) T-type Ca(2+) (I(Ca)T) and NaN/Nav1.9 currents regulate DRG neurons by setting the threshold for the action potential. Although alterations in these channels have been implicated in a variety of pathological pain states, their roles in processing sensory information remai...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151607/ https://www.ncbi.nlm.nih.gov/pubmed/17190903 http://dx.doi.org/10.1085/jgp.200609665 |
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author | Coste, Bertrand Crest, Marcel Delmas, Patrick |
author_facet | Coste, Bertrand Crest, Marcel Delmas, Patrick |
author_sort | Coste, Bertrand |
collection | PubMed |
description | Low voltage–activated (LVA) T-type Ca(2+) (I(Ca)T) and NaN/Nav1.9 currents regulate DRG neurons by setting the threshold for the action potential. Although alterations in these channels have been implicated in a variety of pathological pain states, their roles in processing sensory information remain poorly understood. Here, we carried out a detailed characterization of LVA currents in DRG neurons by using a method for better separation of NaN/Nav1.9 and I(Ca)T currents. NaN/Nav1.9 was inhibited by inorganic I(Ca) blockers as follows (IC(50), μM): La(3+) (46) > Cd(2+) (233) > Ni(2+) (892) and by mibefradil, a non-dihydropyridine I(Ca)T antagonist. Amiloride, however, a preferential Cav3.2 channel blocker, had no effects on NaN/Nav1.9 current. Using these discriminative tools, we showed that NaN/Nav1.9, Cav3.2, and amiloride- and Ni(2+)-resistant I(Ca)T (AR-I(Ca)T) contribute differentially to LVA currents in distinct sensory cell populations. NaN/Nav1.9 carried LVA currents into type-I (CI) and type-II (CII) small nociceptors and medium-Aδ–like nociceptive cells but not in low-threshold mechanoreceptors, including putative Down-hair (D-hair) and Aα/β cells. Cav3.2 predominated in CII-nociceptors and in putative D-hair cells. AR-I(Ca)T was restricted to CII-nociceptors, putative D-hair cells, and Aα/β-like cells. These cell types distinguished by their current-signature displayed different types of mechanosensitive channels. CI- and CII-nociceptors displayed amiloride-sensitive high-threshold mechanical currents with slow or no adaptation, respectively. Putative D-hair and Aα/β-like cells had low-threshold mechanical currents, which were distinguished by their adapting kinetics and sensitivity to amiloride. Thus, subspecialized DRG cells express specific combinations of LVA and mechanosensitive channels, which are likely to play a key role in shaping responses of DRG neurons transmitting different sensory modalities. |
format | Text |
id | pubmed-2151607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21516072008-01-17 Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons Coste, Bertrand Crest, Marcel Delmas, Patrick J Gen Physiol Articles Low voltage–activated (LVA) T-type Ca(2+) (I(Ca)T) and NaN/Nav1.9 currents regulate DRG neurons by setting the threshold for the action potential. Although alterations in these channels have been implicated in a variety of pathological pain states, their roles in processing sensory information remain poorly understood. Here, we carried out a detailed characterization of LVA currents in DRG neurons by using a method for better separation of NaN/Nav1.9 and I(Ca)T currents. NaN/Nav1.9 was inhibited by inorganic I(Ca) blockers as follows (IC(50), μM): La(3+) (46) > Cd(2+) (233) > Ni(2+) (892) and by mibefradil, a non-dihydropyridine I(Ca)T antagonist. Amiloride, however, a preferential Cav3.2 channel blocker, had no effects on NaN/Nav1.9 current. Using these discriminative tools, we showed that NaN/Nav1.9, Cav3.2, and amiloride- and Ni(2+)-resistant I(Ca)T (AR-I(Ca)T) contribute differentially to LVA currents in distinct sensory cell populations. NaN/Nav1.9 carried LVA currents into type-I (CI) and type-II (CII) small nociceptors and medium-Aδ–like nociceptive cells but not in low-threshold mechanoreceptors, including putative Down-hair (D-hair) and Aα/β cells. Cav3.2 predominated in CII-nociceptors and in putative D-hair cells. AR-I(Ca)T was restricted to CII-nociceptors, putative D-hair cells, and Aα/β-like cells. These cell types distinguished by their current-signature displayed different types of mechanosensitive channels. CI- and CII-nociceptors displayed amiloride-sensitive high-threshold mechanical currents with slow or no adaptation, respectively. Putative D-hair and Aα/β-like cells had low-threshold mechanical currents, which were distinguished by their adapting kinetics and sensitivity to amiloride. Thus, subspecialized DRG cells express specific combinations of LVA and mechanosensitive channels, which are likely to play a key role in shaping responses of DRG neurons transmitting different sensory modalities. The Rockefeller University Press 2007-01 /pmc/articles/PMC2151607/ /pubmed/17190903 http://dx.doi.org/10.1085/jgp.200609665 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Coste, Bertrand Crest, Marcel Delmas, Patrick Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons |
title | Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons |
title_full | Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons |
title_fullStr | Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons |
title_full_unstemmed | Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons |
title_short | Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca(2+) Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons |
title_sort | pharmacological dissection and distribution of nan/nav1.9, t-type ca(2+) currents, and mechanically activated cation currents in different populations of drg neurons |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151607/ https://www.ncbi.nlm.nih.gov/pubmed/17190903 http://dx.doi.org/10.1085/jgp.200609665 |
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