Effects of endogenous cannabinoid anandamide on excitation–contraction coupling in rat ventricular myocytes |
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Authors: | Lina T Al Kury Oleg I Voitychuk Ramiz M Ali Sehamuddin Galadari Keun-Hang Susan Yang Frank Christopher Howarth Yaroslav M Shuba Murat Oz |
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Institution: | 1. Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates;2. Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates;3. Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates;4. Bogomoletz Institute of Physiology and International Center of Molecular Physiology, National Academy of Sciences of Ukraine, Kyiv-24, Ukraine;5. Department of Biological Sciences, Schmid College of Science and Engineering, Chapman University, One University Drive, Orange, CA 92866, USA |
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Abstract: | 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. |
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Keywords: | AP action potential APD action potential duration APD60 action potential duration at 60% level of repolarization AMP amplitude AA arachidonic acid APIII antipyrylazo III BSA bovine serum albumin DMSO dimethylsulphoxide DHP dihydropyridine NAEs N-acylethanolamines AEA N-arachidonoyl ethanolamide anandamide NEM N-ethylmaleimide NO nitric oxide NT normal tyrode PTX pertussis toxin RCL resting cell length metAEA R-methanandamide SR sarcoplasmic reticulum THALF time from peak to half TPK time to peak TRP transient-receptor potential |
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