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Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels
BACKGROUND: Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggeste...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292985/ https://www.ncbi.nlm.nih.gov/pubmed/22233604 http://dx.doi.org/10.1186/1744-8069-8-2 |
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author | Lee, Jaekwang Kim, Taekeun Hong, Jinpyo Woo, Junsung Min, Hyunjung Hwang, Eunmi Lee, Sung Joong Lee, C Justin |
author_facet | Lee, Jaekwang Kim, Taekeun Hong, Jinpyo Woo, Junsung Min, Hyunjung Hwang, Eunmi Lee, Sung Joong Lee, C Justin |
author_sort | Lee, Jaekwang |
collection | PubMed |
description | BACKGROUND: Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons. FINDINGS: When IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K(+ )channels, K(v)1.1 and K(v)1.2 (voltage-gated K(+ )channels) and TREK1 and TRAAK (K(2P )channels). IQ effectively reduced the currents mediated by both K(+ )channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K(v)1.1 and K(v)1.2. CONCLUSIONS: Our results demonstrate that IQ blocks the voltage-gated K(+ )channels to increase AP duration and K(2P )channels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus. |
format | Online Article Text |
id | pubmed-3292985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32929852012-03-05 Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels Lee, Jaekwang Kim, Taekeun Hong, Jinpyo Woo, Junsung Min, Hyunjung Hwang, Eunmi Lee, Sung Joong Lee, C Justin Mol Pain Short Report BACKGROUND: Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons. FINDINGS: When IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K(+ )channels, K(v)1.1 and K(v)1.2 (voltage-gated K(+ )channels) and TREK1 and TRAAK (K(2P )channels). IQ effectively reduced the currents mediated by both K(+ )channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K(v)1.1 and K(v)1.2. CONCLUSIONS: Our results demonstrate that IQ blocks the voltage-gated K(+ )channels to increase AP duration and K(2P )channels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus. BioMed Central 2012-01-11 /pmc/articles/PMC3292985/ /pubmed/22233604 http://dx.doi.org/10.1186/1744-8069-8-2 Text en Copyright ©2012 Lee et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Report Lee, Jaekwang Kim, Taekeun Hong, Jinpyo Woo, Junsung Min, Hyunjung Hwang, Eunmi Lee, Sung Joong Lee, C Justin Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels |
title | Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels |
title_full | Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels |
title_fullStr | Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels |
title_full_unstemmed | Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels |
title_short | Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels |
title_sort | imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (k(2p)) and voltage-gated (k(v)1.1 and k(v)1.2) potassium channels |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292985/ https://www.ncbi.nlm.nih.gov/pubmed/22233604 http://dx.doi.org/10.1186/1744-8069-8-2 |
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