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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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Detalles Bibliográficos
Autores principales: Coste, Bertrand, Crest, Marcel, Delmas, Patrick
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
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.
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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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