Effects of endogenous cannabinoid anandamide on excitation-contraction coupling in rat ventricular myocytes.
A role for anandamide (N-arachidonoyl ethanolamide; AEA), a major endocannabinoid, in the cardiovascular system in various pathological conditions has been reported in earlier reports. In the present study, the effects of AEA on contractility, Ca2+ signaling, and action potential (AP) characteristics were investigated in rat ventricular myocytes. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the fluorescent indicator fura-2 AM. AEA (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 electrically evoked Ca2+ transients following caffeine application were not altered. Biochemical studies in sarcoplasmic reticulum (SR) vesicles from rat ventricles indicated that AEA affected Ca2+ -uptake and Ca2+ -ATPase activity in a biphasic manner. [3H]-ryanodine binding and passive Ca2+ release from SR vesicles were not altered by 10 μM AEA. Whole-cell patch-clamp technique was employed to investigate the effect of AEA on the characteristics of APs. AEA (1 μM) significantly decreased the duration of AP. The effect of AEA on myocyte shortening and AP characteristics was not altered in the presence of pertussis toxin (PTX, 2 μg/ml for 4 h), AM251 and SR141716 (cannabinoid type 1 receptor antagonists; 0.3 μM) or AM630 and SR 144528 (cannabinoid type 2 receptor antagonists; 0.3 μM). The results suggest that AEA depresses ventricular myocyte contractility by decreasing the action potential duration (APD) in a manner independent of CB1 and CB2 receptors.
Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
Lina T
LT
Al Kury
Bogomoletz Institute of Physiology and International Center of Molecular Physiology, National Academy of Sciences of Ukraine, Kyiv-24, Ukraine.
Oleg I
OI
Voitychuk
Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
Ramiz M
RM
Ali
Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
Sehamuddin
S
Galadari
Department of Biological Sciences, Schmid College of Science and Engineering, Chapman University, One University Drive, Orange, CA 92866, USA.
Keun-Hang Susan
KH
Yang
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
Frank Christopher
FC
Howarth
Bogomoletz Institute of Physiology and International Center of Molecular Physiology, National Academy of Sciences of Ukraine, Kyiv-24, Ukraine.
Yaroslav M
YM
Shuba
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.
Murat
M
Oz
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D063388:Endocannabinoids / Q000494:pharmacology*; D016257:Fura-2 / Q000737:chemistry; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D037342:Pertussis Toxin / Q000633:toxicity; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism
D001095:Arachidonic Acids; D063388:Endocannabinoids; D007211:Indoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D002110:Caffeine; C103505:AM 251; D037342:Pertussis Toxin; D002118:Calcium; D016257:Fura-2; C094023:iodopravadoline; C078814:anandamide
Anandamide; Contraction; Endocannabinoid; Intracellular calcium; Ventricular action potential; Ventricular myocytes