title: Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.
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 Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1μM) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca(2+) transients. However, the amplitudes of caffeine-evoked Ca(2+) transients and the rate of recovery of electrically evoked Ca(2+) transients following caffeine application were not altered. CBD (1μM) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1μM in a voltage-independent manner. Radioligand studies indicated that the specific binding of [(3)H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca(2+) channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes.
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Ramez M
authors.initials: RM
authors.lastname: Ali
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates; Department of Natural Science and Public Health, College of Sustainability Sciences and Humanities, Zayed University, Abu Dhabi, United Arab Emirates.
authors.forename: Lina T
authors.initials: LT
authors.lastname: Al Kury
authors.affiliation: Department of Biological Sciences, Schmid College of Science and Engineering, Chapman University, One University Drive, Orange, CA 92866, USA.
authors.forename: Keun-Hang Susan
authors.initials: KH
authors.lastname: Yang
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Anwar
authors.initials: A
authors.lastname: Qureshi
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Rajesh
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Sehamuddin
authors.initials: S
authors.lastname: Galadari
authors.affiliation: Bogomoletz Institute of Physiology and International Center of Molecular Physiology, National Academy of Sciences of Ukraine, Kyiv-24, Ukraine.
authors.forename: Yaroslav M
authors.initials: YM
authors.lastname: Shuba
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Frank Christopher
authors.initials: FC
authors.lastname: Howarth
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates. Electronic address: murat_oz@uaeu.ac.ae.
authors.forename: Murat
authors.initials: M
authors.lastname: Oz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002185:Cannabidiol / Q000494:pharmacology*; D002188:Cannabis; D002478:Cells, Cultured; D056966:Excitation Contraction Coupling / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020746:Calcium Channels, L-Type; D002185:Cannabidiol; D002118:Calcium
keywords: Calcium channels; Cannabidiol; Cannabinoid; Contraction; Intracellular calcium; Ventricular myocytes