Document Type

Article

Publication Date

4-2015

Abstract

Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the Ca2+ sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca2+ currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1 μM) caused a significant decrease in the amplitudes of electrically-evoked myocyte shortening and Ca2+ transients. However, the amplitudes of caffeine-evoked Ca2+ transients and the rate of recovery of electricallyevoked Ca2+ transients following caffeine application were not altered. Whole-cell patch-clamp technique was employed to investigate the effect of CBD on the characteristics of action potentials (APs) and L-type Ca2+ channels. CBD (1 μM) significantly decreased the duration of APs. Further studies on L-type Ca2+ channels indicated that CBD inhibits these channels with IC50 of 0.1 μM in a voltage-independent manner. Radioligand studies indicated that the specific binding of [3H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca2+ channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Cell Calcium. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cell Calcium, volume 57, in 2015. DOI: 10.1016/j.ceca.2015.02.001

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Peer Reviewed

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Copyright

Elsevier

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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