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Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation

IB4-positive maxillary trigeminal ganglion (TG) neurons are a subtype of afferent neurons involving nociception in orofacial regions, and excitability of these neurons is associated with orofacial nociceptive sensitivity. TREK-2 channel is a member of two-pore domain potassium (K2P) channel family m...

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Autores principales: Chang, Ya-Ting, Ling, Jennifer, Gu, Jianguo G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411610/
https://www.ncbi.nlm.nih.gov/pubmed/34461754
http://dx.doi.org/10.1177/17448069211042963
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author Chang, Ya-Ting
Ling, Jennifer
Gu, Jianguo G
author_facet Chang, Ya-Ting
Ling, Jennifer
Gu, Jianguo G
author_sort Chang, Ya-Ting
collection PubMed
description IB4-positive maxillary trigeminal ganglion (TG) neurons are a subtype of afferent neurons involving nociception in orofacial regions, and excitability of these neurons is associated with orofacial nociceptive sensitivity. TREK-2 channel is a member of two-pore domain potassium (K2P) channel family mediating leak K(+) currents. It has been shown previously that TREK-2 channel activity can be enhanced following GABAB receptor activation, leading to a reduction of cortical neuron excitability. In the present study, we have characterized TREK-2 channel expression on maxillary TG neurons and investigated the effect of the GABAB agonist baclofen on electrophysiological properties of small-sized maxillary TG neurons of rats. We show with immunohistochemistry that TREK-2 channels are predominantly expressed in small-sized IB4-positive maxillary TG neurons. Patch-clamp recordings on neurons in ex vivo TG preparations show that baclofen hyperpolarizes resting membrane potentials, increases outward leak currents, and decreases input resistances in IB4-positive maxillary TG neurons. Moreover, baclofen significantly reduces action potential (AP) firing in IB4-positive maxillary TG neurons. In contrast, baclofen shows no significant effect on electrophysiological properties of small-sized nociceptive-like and non-nociceptive-like maxillary trigeminal neurons that are IB4-negatve. Our results suggest that TREK-2 channel activity can be enhanced by baclofen, leading to reduced excitability of IB4-positive maxillary TG neurons. This finding provides new insights into the role of TREK-2 and GABAB receptors in controlling nociceptive sensitivity in orofacial regions, which may have therapeutic implications.
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spelling pubmed-84116102021-09-03 Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation Chang, Ya-Ting Ling, Jennifer Gu, Jianguo G Mol Pain Research Article IB4-positive maxillary trigeminal ganglion (TG) neurons are a subtype of afferent neurons involving nociception in orofacial regions, and excitability of these neurons is associated with orofacial nociceptive sensitivity. TREK-2 channel is a member of two-pore domain potassium (K2P) channel family mediating leak K(+) currents. It has been shown previously that TREK-2 channel activity can be enhanced following GABAB receptor activation, leading to a reduction of cortical neuron excitability. In the present study, we have characterized TREK-2 channel expression on maxillary TG neurons and investigated the effect of the GABAB agonist baclofen on electrophysiological properties of small-sized maxillary TG neurons of rats. We show with immunohistochemistry that TREK-2 channels are predominantly expressed in small-sized IB4-positive maxillary TG neurons. Patch-clamp recordings on neurons in ex vivo TG preparations show that baclofen hyperpolarizes resting membrane potentials, increases outward leak currents, and decreases input resistances in IB4-positive maxillary TG neurons. Moreover, baclofen significantly reduces action potential (AP) firing in IB4-positive maxillary TG neurons. In contrast, baclofen shows no significant effect on electrophysiological properties of small-sized nociceptive-like and non-nociceptive-like maxillary trigeminal neurons that are IB4-negatve. Our results suggest that TREK-2 channel activity can be enhanced by baclofen, leading to reduced excitability of IB4-positive maxillary TG neurons. This finding provides new insights into the role of TREK-2 and GABAB receptors in controlling nociceptive sensitivity in orofacial regions, which may have therapeutic implications. SAGE Publications 2021-08-30 /pmc/articles/PMC8411610/ /pubmed/34461754 http://dx.doi.org/10.1177/17448069211042963 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Chang, Ya-Ting
Ling, Jennifer
Gu, Jianguo G
Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation
title Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation
title_full Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation
title_fullStr Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation
title_full_unstemmed Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation
title_short Effects of GABA(B) receptor activation on excitability of IB4-positive maxillary trigeminal ganglion neurons: Possible involvement of TREK2 activation
title_sort effects of gaba(b) receptor activation on excitability of ib4-positive maxillary trigeminal ganglion neurons: possible involvement of trek2 activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411610/
https://www.ncbi.nlm.nih.gov/pubmed/34461754
http://dx.doi.org/10.1177/17448069211042963
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