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The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations

Cannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on acti...

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Autores principales: Topal, Leila, Naveed, Muhammad, Orvos, Péter, Pászti, Bence, Prorok, János, Bajtel, Ákos, Kiss, Tivadar, Csupor-Löffler, Boglárka, Csupor, Dezső, Baczkó, István, Varró, András, Virág, László, Jost, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241752/
https://www.ncbi.nlm.nih.gov/pubmed/34031697
http://dx.doi.org/10.1007/s00204-021-03086-0
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author Topal, Leila
Naveed, Muhammad
Orvos, Péter
Pászti, Bence
Prorok, János
Bajtel, Ákos
Kiss, Tivadar
Csupor-Löffler, Boglárka
Csupor, Dezső
Baczkó, István
Varró, András
Virág, László
Jost, Norbert
author_facet Topal, Leila
Naveed, Muhammad
Orvos, Péter
Pászti, Bence
Prorok, János
Bajtel, Ákos
Kiss, Tivadar
Csupor-Löffler, Boglárka
Csupor, Dezső
Baczkó, István
Varró, András
Virág, László
Jost, Norbert
author_sort Topal, Leila
collection PubMed
description Cannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (I(Kr)) and slow (I(Ks)) delayed rectifier, the transient outward (I(to)) and inward rectifier (I(K1)) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased I(Kr), I(Ks) and I(to) (only in dog) significantly with corresponding estimated EC(50) values of 4.9, 3.1 and 5 µM, respectively, without changing I(K1). Although the EC(50) value of CBD was found to be higher than literary C(max) values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired.
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spelling pubmed-82417522021-07-14 The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations Topal, Leila Naveed, Muhammad Orvos, Péter Pászti, Bence Prorok, János Bajtel, Ákos Kiss, Tivadar Csupor-Löffler, Boglárka Csupor, Dezső Baczkó, István Varró, András Virág, László Jost, Norbert Arch Toxicol Organ Toxicity and Mechanisms Cannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (I(Kr)) and slow (I(Ks)) delayed rectifier, the transient outward (I(to)) and inward rectifier (I(K1)) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased I(Kr), I(Ks) and I(to) (only in dog) significantly with corresponding estimated EC(50) values of 4.9, 3.1 and 5 µM, respectively, without changing I(K1). Although the EC(50) value of CBD was found to be higher than literary C(max) values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired. Springer Berlin Heidelberg 2021-05-24 2021 /pmc/articles/PMC8241752/ /pubmed/34031697 http://dx.doi.org/10.1007/s00204-021-03086-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Organ Toxicity and Mechanisms
Topal, Leila
Naveed, Muhammad
Orvos, Péter
Pászti, Bence
Prorok, János
Bajtel, Ákos
Kiss, Tivadar
Csupor-Löffler, Boglárka
Csupor, Dezső
Baczkó, István
Varró, András
Virág, László
Jost, Norbert
The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations
title The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations
title_full The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations
title_fullStr The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations
title_full_unstemmed The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations
title_short The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations
title_sort electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations
topic Organ Toxicity and Mechanisms
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241752/
https://www.ncbi.nlm.nih.gov/pubmed/34031697
http://dx.doi.org/10.1007/s00204-021-03086-0
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