title: Effects of endogenous cannabinoid anandamide on cardiac Na⁺/Ca²⁺ exchanger.
abstract: Endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) has been shown to cause negative inotropic and antiarrhythmic effects in ventricular myocytes. In this study, using whole-cell patch clamp technique, we have investigated the effects of AEA on cardiac Na(+)/Ca(2+) exchanger (NCX1)-mediated currents. AEA suppressed NCX1 with an IC50 value of 4.7 μM. Both inward and outward components of exchanger currents were suppressed by AEA equally. AEA inhibition was mimicked by the metabolically stable analogue, methanandamide (metAEA, 10 μM) while it was not influenced by inhibition of fatty acid amide hydrolase with 1 μM URB597 incubation. The effect of AEA, was not altered in the presence of cannabinoid receptor 1 and 2 antagonists AM251 (1 μM) and AM630 (1 μM), respectively. In addition, inhibition by AEA remained unchanged after pertussis toxin (PTX, 2 μg/ml) treatment or following the inclusion of GDP-β-S (1 mM) in pipette solution. Currents mediated by NCX1 expressed in HEK-293 cells were also inhibited by 10 μM AEA a partially reversible manner. Confocal microscopy images indicated that the intensity of YFP-NCX1 expression on cell surface was not altered by AEA. Collectively, the results indicate that AEA directly inhibits the function of NCX1 in rat ventricular myocytes and in HEK-293 cells expressing NCX1.
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, 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 Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Faisal T
authors.initials: FT
authors.lastname: Thayyullathil
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Rajesh
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Ramez M
authors.initials: RM
authors.lastname: Ali
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, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Frank Christopher
authors.initials: FC
authors.lastname: Howarth
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Sehamuddin
authors.initials: S
authors.lastname: Galadari
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates. Electronic address: murat_oz@uaeu.ac.ae.
authors.forename: Murat
authors.initials: M
authors.lastname: Oz
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002478:Cells, Cultured; D063388:Endocannabinoids / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D001549:Benzamides; D002121:Calcium Channel Blockers; D002219:Carbamates; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D019831:Sodium-Calcium Exchanger; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C078814:anandamide
keywords: Anandamide; Na(+)/Ca(2+) exchanger; Whole-cell patch clamp technique