Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

THE ELECTROPHYSIOLOGICAL EFFECTS OF CANNABIDIOL ON ACTION POTENTIAL AND TRANSMEMBRANE POTASSIUM CURRENTS IN DOG AND RABBIT CARDIAC PREPARATIONS M. Naveed 1 , L. Topal 1 , J. Prorok 1 , B. Pászti 1 , D. Csupor 2 , I. Baczkó 1 , L. Virág 1 , N. Jost 1 , A. Varró 1 1 Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Hungary; 2 Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Hungary 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 (IKr) and slow (IKs) delayed rectifier, the transient outward (Ito) and inward rectifier (IK1) potassium currents in rabbit and dog cardiac preparations. CBD increased action pote ntial 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 IKr, IKs and Ito (only in dog) significan tly with corresponding estimated IC50 values of 4.9, 3.1 and 5 μM, respectively, without changing IK1. Although the IC50 value of CBD was found to be higher than literary Cmax 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.

Keywords: cannabidiol, electrophysiology, action potential, potassium currents, rabbit, dog

Funding:Financial support from the Economic Development and Innovation Operative Programme GINOP-2.3.2-15-2016-00012, the National Research Development and Innovation Office (NKFIH K 135464 and NKFIH K 128851), the Ministry of Human Capacities Hungary (20391-3/2018/FEKUSTRAT and EFOP-3.6.2-16-2017- 00006), and from the Eötvös Loránd Research Network are gratefully acknowledged.

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