The electrophysiological effect of cannabidiol on hERG current and in guinea-pig and rabbit cardiac preparations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-09-30

AUTHORS

Péter Orvos, Bence Pászti, Leila Topal, Péter Gazdag, János Prorok, Alexandra Polyák, Tivadar Kiss, Edit Tóth-Molnár, Boglárka Csupor-Löffler, Ákos Bajtel, András Varró, Judit Hohmann, László Virág, Dezső Csupor

ABSTRACT

Cannabis use is associated with cardiovascular adverse effects ranging from arrhythmias to sudden cardiac death. The exact mechanism of action behind these activities is unknown. The aim of our work was to study the effect of cannabidiol (CBD), tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol on cellular cardiac electrophysiological properties including ECG parameters, action potentials, hERG and IKr ion channels in HEK cell line and in rabbit and guinea pig cardiac preparations. CBD increased action potential duration in rabbit and guinea pig right ventricular papillary muscle at lower concentrations (1 µM, 2.5 µM and 5 µM) but did not significantly change it at 10 µM. CBD at high concentration (10 µM) decreased inward late sodium and L-type calcium currents as well. CBD inhibited hERG potassium channels with an IC50 value of 2.07 µM at room temperature and delayed rectifier potassium current with 6.5 µM at 37 °C, respectively. The frequency corrected QT interval (QTc) was significantly lengthened in anaesthetized guinea pig without significantly changing other ECG parameters. Although the IC50 value of CBD was higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that hERG and potassium channel inhibition might have a role in the possible proarrhythmic adverse effects of cannabinoids in situations where metabolism of CBD impaired and/or the repolarization reserve is weakened. More... »

PAGES

16079

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-020-73165-2

DOI

http://dx.doi.org/10.1038/s41598-020-73165-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1131322523

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32999428


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25 schema:description Cannabis use is associated with cardiovascular adverse effects ranging from arrhythmias to sudden cardiac death. The exact mechanism of action behind these activities is unknown. The aim of our work was to study the effect of cannabidiol (CBD), tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol on cellular cardiac electrophysiological properties including ECG parameters, action potentials, hERG and IKr ion channels in HEK cell line and in rabbit and guinea pig cardiac preparations. CBD increased action potential duration in rabbit and guinea pig right ventricular papillary muscle at lower concentrations (1 µM, 2.5 µM and 5 µM) but did not significantly change it at 10 µM. CBD at high concentration (10 µM) decreased inward late sodium and L-type calcium currents as well. CBD inhibited hERG potassium channels with an IC50 value of 2.07 µM at room temperature and delayed rectifier potassium current with 6.5 µM at 37 °C, respectively. The frequency corrected QT interval (QTc) was significantly lengthened in anaesthetized guinea pig without significantly changing other ECG parameters. Although the IC50 value of CBD was higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that hERG and potassium channel inhibition might have a role in the possible proarrhythmic adverse effects of cannabinoids in situations where metabolism of CBD impaired and/or the repolarization reserve is weakened.
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33 ECG parameters
34 HEK cell lines
35 IC50 values
36 L-type calcium current
37 QT interval
38 action
39 action potential duration
40 action potentials
41 activity
42 adverse effects
43 aim
44 arrhythmias
45 calcium current
46 cannabidiol
47 cannabinoids
48 cannabis use
49 cardiac death
50 cardiac electrophysiological properties
51 cardiac preparations
52 cardiovascular adverse effects
53 cell lines
54 channel inhibition
55 channels
56 concentration
57 current
58 death
59 duration
60 effect
61 effects of cannabidiol
62 electrophysiological effects
63 electrophysiological properties
64 exact mechanism
65 frequency
66 guinea pig cardiac preparations
67 guinea pig right ventricular papillary muscles
68 guinea pigs
69 hERG
70 hERG potassium channel
71 high concentrations
72 inhibition
73 intake
74 interval
75 ion channels
76 late sodium
77 lines
78 low concentrations
79 mechanism
80 metabolism
81 metabolism of cannabidiol
82 muscle
83 oral intake
84 papillary muscles
85 parameters
86 pigs
87 possibility
88 potassium
89 potassium channel inhibition
90 potassium channels
91 potential
92 potential duration
93 preparation
94 properties
95 rabbit cardiac preparations
96 rabbits
97 rectifier potassium
98 repolarization reserve
99 reserves
100 results
101 right ventricular papillary muscles
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