Cannabidiol activates neuronal Kv7 channels

Cannabidiol (CBD), a chemical found in the Cannabis sativa plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and found enhancement of flux through heterologously expressed human...

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Detalles Bibliográficos
Autores principales: Zhang, Han-Xiong Bear, Heckman, Laurel, Niday, Zachary, Jo, Sooyeon, Fujita, Akie, Shim, Jaehoon, Pandey, Roshan, Al Jandal, Hoor, Jayakar, Selwyn, Barrett, Lee B, Smith, Jennifer, Woolf, Clifford J, Bean, Bruce P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Neuroscience
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856652/
https://www.ncbi.nlm.nih.gov/pubmed/35179483
http://dx.doi.org/10.7554/eLife.73246
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author Zhang, Han-Xiong Bear
Heckman, Laurel
Niday, Zachary
Jo, Sooyeon
Fujita, Akie
Shim, Jaehoon
Pandey, Roshan
Al Jandal, Hoor
Jayakar, Selwyn
Barrett, Lee B
Smith, Jennifer
Woolf, Clifford J
Bean, Bruce P
author_facet Zhang, Han-Xiong Bear
Heckman, Laurel
Niday, Zachary
Jo, Sooyeon
Fujita, Akie
Shim, Jaehoon
Pandey, Roshan
Al Jandal, Hoor
Jayakar, Selwyn
Barrett, Lee B
Smith, Jennifer
Woolf, Clifford J
Bean, Bruce P
author_sort Zhang, Han-Xiong Bear
collection PubMed
description Cannabidiol (CBD), a chemical found in the Cannabis sativa plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and found enhancement of flux through heterologously expressed human Kv7.2/7.3 channels by CBD. Patch-clamp recordings showed that CBD acts at submicromolar concentrations to shift the voltage dependence of Kv7.2/7.3 channels in the hyperpolarizing direction, producing a dramatic enhancement of current at voltages near –50 mV. CBD enhanced native M-current in mouse superior cervical ganglion starting at concentrations of 30 nM and also enhanced M-current in rat hippocampal neurons. The potent enhancement of Kv2/7.3 channels by CBD may contribute to its effectiveness as an antiepileptic drug by reducing neuronal hyperexcitability.
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spelling pubmed-88566522022-02-22 Cannabidiol activates neuronal Kv7 channels Zhang, Han-Xiong Bear Heckman, Laurel Niday, Zachary Jo, Sooyeon Fujita, Akie Shim, Jaehoon Pandey, Roshan Al Jandal, Hoor Jayakar, Selwyn Barrett, Lee B Smith, Jennifer Woolf, Clifford J Bean, Bruce P eLife Neuroscience Cannabidiol (CBD), a chemical found in the Cannabis sativa plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and found enhancement of flux through heterologously expressed human Kv7.2/7.3 channels by CBD. Patch-clamp recordings showed that CBD acts at submicromolar concentrations to shift the voltage dependence of Kv7.2/7.3 channels in the hyperpolarizing direction, producing a dramatic enhancement of current at voltages near –50 mV. CBD enhanced native M-current in mouse superior cervical ganglion starting at concentrations of 30 nM and also enhanced M-current in rat hippocampal neurons. The potent enhancement of Kv2/7.3 channels by CBD may contribute to its effectiveness as an antiepileptic drug by reducing neuronal hyperexcitability. eLife Sciences Publications, Ltd 2022-02-18 /pmc/articles/PMC8856652/ /pubmed/35179483 http://dx.doi.org/10.7554/eLife.73246 Text en © 2022, Zhang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Zhang, Han-Xiong Bear
Heckman, Laurel
Niday, Zachary
Jo, Sooyeon
Fujita, Akie
Shim, Jaehoon
Pandey, Roshan
Al Jandal, Hoor
Jayakar, Selwyn
Barrett, Lee B
Smith, Jennifer
Woolf, Clifford J
Bean, Bruce P
Cannabidiol activates neuronal Kv7 channels
title Cannabidiol activates neuronal Kv7 channels
title_full Cannabidiol activates neuronal Kv7 channels
title_fullStr Cannabidiol activates neuronal Kv7 channels
title_full_unstemmed Cannabidiol activates neuronal Kv7 channels
title_short Cannabidiol activates neuronal Kv7 channels
title_sort cannabidiol activates neuronal kv7 channels
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856652/
https://www.ncbi.nlm.nih.gov/pubmed/35179483
http://dx.doi.org/10.7554/eLife.73246
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